Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([S:4][CH2:5][CH:6]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:7]([NH:9][CH2:10][C:11]([OH:13])=O)=[O:8])(=[O:3])[CH3:2].C(N(CC)CC)C.ClC(OCC)=O.[CH3:31][N:32]([CH3:36])[CH2:33][CH2:34][NH2:35].N1C(=O)CC(=O)NC1=O>C(Cl)Cl.CO>[C:1]([S:4][CH2:5][CH:6]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:7]([NH:9][CH2:10][C:11]([NH:35][CH2:34][CH2:33][N:32]([CH3:36])[CH3:31])=[O:13])=[O:8])(=[O:3])[CH3:2]
Reactant: CN(C)CCN
Reactant: CC(=O)SCC(CC(C)C)C(=O)NCC(=O)O
Agent: CCOC(=O)Cl
Agent: O=C1CC(=O)NC(=O)N1
Solvent: CCN(CC)CC
Solvent: CO
Solvent: ClCCl
Product: CC(=O)SCC(CC(C)C)C(=O)NCC(=O)NCCN(C)C
Temperature: -10 °C
Reaction time: 0.5 h

Procedure:
A 2.61 g (0.01 mole) sample of (±)-N-[2-(acetylmercaptomethyl)-4-methyl-1-oxopentyl]glycine is slurried in 50 ml of CH2Cl2. Triethylamine (1.08 g, 0.01 mole) is added to give a solution which is cooled to -10° C. and treated with 1.08 g (0.01 mole) of ethyl chloroformate. After 1/2 hour, a solution of N,N-dimethylethylenediamine (0.88 g, 0.01 mole) in 10 ml of CH2Cl2 is added, and stirring from -5° C. to +25° C. continued for 2 hours. The mixture is evaporated and triturated with ethyl acetate. The triethylamine hydrochloride is filtered and the filtrates evaporated to an oil, 3.6 g. A 2.95 g sample of oil is dissolved with 1 equivalent of barbituric acid in methanol, filtered and evaporated to a foam. Addition of acetonitrile gives a white solid which is washed (briefly) with absolute ethanol and then acetonitrile. Recrystallization from 100 ml of acetonitrile gives a white powder, 1.3 g of (±)-N2 -[2-[(acetylthio)methyl]-4-methyl-1-oxopentyl]-N-[2-(dimethylamino)ethyl]glycinamide, barbituric acid (1:1) salt (34%), m.p. 151°-154°, which analyzes correctly for a salt with 1.0 mole of barbituric acid and 0.5 mole of water.
Reaction SMILES: O.C[O-].[Na+].[SH:5][CH:6]([C:10](=[O:15])[CH2:11][CH:12]([CH3:14])[CH3:13])[CH:7]([CH3:9])[CH3:8].Cl[CH:17]([C:20](=[O:24])[CH2:21][CH2:22][CH3:23])[CH2:18][CH3:19]>CO>[CH:7]([CH:6]([S:5][CH:17]([CH2:18][CH3:19])[C:20]([CH2:21][CH2:22][CH3:23])=[O:24])[C:10]([CH2:11][CH:12]([CH3:14])[CH3:13])=[O:15])([CH3:9])[CH3:8]
Reactant: CC(C)CC(=O)C(S)C(C)C
Reactant: CCCC(=O)C(Cl)CC
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CCCC(=O)C(CC)SC(C(=O)CC(C)C)C(C)C
Reaction time: 0.03 h

Procedure:
Into a 50 ml, round bottom, three-necked flask equipped with magnetic stirrer, pot thermometer, "Y" tube, nitrogen inlet tube, reflux condenser with cotton plug, and water bath is placed a solution of 0.65 grams (0.012 moles) of sodium methoxide dissolved in 10 ml anhydrous methanol. While maintaining the temperature of the reaction mass at 24°-27° C, a solution of 2.1 grams of 3-mercapto-2,6-dimethyl-4-heptanone dissolved in 12 ml. anhydrous methanol is added to the sodium methoxide solution. 1.78 grams of 3-chloro-4-heptanone is then added to the reaction mass with stirring over a period of 2 minutes, the reaction mass temperature rising to 38° C. Two ml anhydrous methanol used as rinse is then added to the reaction mass, and with stirring the reaction mass temperature cools to 25° C. The reaction mass is continued to be stirred at 25° C for a period of 5 hours. At this point 25 ml distilled water is added, and the resulting solid dissolves. The oil phase is extracted with three 15 ml portions of methylene chloride, and the extracts are combined and washed with one 10 ml portion of water. The extracts are then dried over anhydrous sodium sulfate and gravity filtered and concentrated on a rotary evaporator using water aspirator vacuum to a weight of 3.20 grams (yellow oil). GLC analysis (8' × 1/4" SE-30 column), NMR, IR and mass spectral analyses of GLC isolated material yield the information that the resulting product is 85% pure and has the structure: ##STR70##
Reaction SMILES: [CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[CH:13][CH:14]=[N:15]3)=[C:10]([O:18][CH2:19][C@:20]3([F:33])[CH2:25][CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21]3)[N:9]=2)[CH:5]=[N:4]1)[CH3:2].FC(F)(F)C(O)=O>C(Cl)Cl.CO>[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[CH:13][CH:14]=[N:15]3)=[C:10]([O:18][CH2:19][C@:20]3([F:33])[CH2:25][CH2:24][CH2:23][NH:22][CH2:21]3)[N:9]=2)[CH:5]=[N:4]1)[CH3:2]
Reactant: CCn1cc(-c2cc3ncccc3c(OC[C@]3(F)CCCN(C(=O)OC(C)(C)C)C3)n2)cn1
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCn1cc(-c2cc3ncccc3c(OC[C@]3(F)CCCNC3)n2)cn1
Temperature: 25 °C
Reaction time: 3 h
Yield: 72.2 %

Procedure:
To a solution of 1,1-dimethylethyl (3S)-3-({[7-(1-ethyl-1H-pyrazol-4-yl)-1,6-naphthyridin-5-yl]oxy}methyl)-3-fluoro-1-piperidinecarboxylate (1.1 g, 2.415 mmol) in DCM (3 ml) was added trifluoroacetic acid (3 ml, 38.9 mmol) and this was stirred at room temp for 3 h. The reaction had gone to completion and so was concentrated in vacuo to yield the crude product. The TFA salt was dissolved in methanol and loaded onto an SCX cartridge (20 g). The impurities were eluted with methanol, and the product was eluted with 2M ammonia in methanol. The filtrate was concentrated in vacuo to yield a cream gummy solid (620 mg). This was purified by large-scale MDAP (Method C). The appropriate vials were combined and concentrated in vacuo to give the product as the TFA salt. To form the free base, this was dissolved in methanol and purified through an SCX cartridge (20 g) eluting with methanol. The product was eluted with 2M ammonia in methanol. The filtrate was concentrated in vacuo to yield the title compound as a clear glass (500 mg).
Reaction SMILES: [F:1][C:2]1[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:20])=[C:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:13]([OH:14])=[C:8]2[CH2:7][CH2:6]1>C1C=CC=CC=1.[O-2].[O-2].[Mn+4]>[F:1][C:2]1[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:20])=[C:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:13]([OH:14])=[C:8]2[CH:7]=[CH:6]1
Reactant: CCOC(=O)c1c(C)nc2c(c1O)CCN2Cc1cccc(F)c1F
Agent: [Mn+4]
Agent: [O-2]
Solvent: c1ccccc1
Product: CCOC(=O)c1c(C)nc2c(ccn2Cc2cccc(F)c2F)c1O
Temperature: 80 °C
Yield: 86.6 %

Procedure:
To a solution of ethyl 1-(2,3-difluorobenzyl)-4-hydroxy-6-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (9.9 g, 27.0 mmol) in benzene (150 mL) was added manganese dioxide (13.81 g, 135 mmol) (activated 85%, 5 micron) and the mixture was heated to 80° C. under nitrogen atmosphere for 3.5 h. The mixture was filtered hot through celite washing with EtOAc (250 mL) and the filtrate was concentrated, dried in vacuo to provide ethyl 1-(2,3-difluorobenzyl)-4-hydroxy-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (9.0 g, 23.39 mmol, 87% yield) as greyish solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.47 (t, J=7.12 Hz, 3 H), 2.84 (s, 3 H), 4.47 (q, J=7.02 Hz, 2 H), 5.51 (s, 2 H), 6.64 (d, J=3.32 Hz, 1 H), 6.79-6.90 (m, 1 H), 6.92-7.03 (m, 2 H), 7.08 (q, J=8.32 Hz, 1 H), 12.78 (s, 1H); LCMS (m/z) ES+=347 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]([CH2:15][C:16]2[O:17][CH:18]=[C:19]([C:21](O)=[O:22])[N:20]=2)[CH3:14])(=[O:12])=[O:11])=[C:5]([CH3:24])[CH:4]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.Cl.[CH3:48][NH:49][CH2:50][C:51]1[CH:62]=[CH:61][C:54]([CH2:55][N:56]2[CH2:59][CH:58]([OH:60])[CH2:57]2)=[CH:53][CH:52]=1>C(Cl)Cl>[OH:60][CH:58]1[CH2:57][N:56]([CH2:55][C:54]2[CH:61]=[CH:62][C:51]([CH2:50][N:49]([CH3:48])[C:21]([C:19]3[N:20]=[C:16]([CH2:15][N:13]([S:10]([C:6]4[C:7]([CH3:9])=[CH:8][C:3]([O:2][CH3:1])=[CH:4][C:5]=4[CH3:24])(=[O:12])=[O:11])[CH3:14])[O:17][CH:18]=3)=[O:22])=[CH:52][CH:53]=2)[CH2:59]1
Reactant: COc1cc(C)c(S(=O)(=O)N(C)Cc2nc(C(=O)O)co2)c(C)c1
Reactant: CNCc1ccc(CN2CC(O)C2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: COc1cc(C)c(S(=O)(=O)N(C)Cc2nc(C(=O)N(C)Cc3ccc(CN4CC(O)C4)cc3)co2)c(C)c1

Procedure:
The title compound was prepared according to general procedure BH using 2-({[(4-methoxy-2,6-dimethylphenyl)sulfonyl](methyl)amino}methyl)-1,3-oxazole-4-carboxylic acid (40 mg, 0.11 mmol), EDCI (29 mg, 0.15 mmol), HOBt (22 mg, 0.16 mmol) DIPEA (0.04 mL, 0.21 mmol), 1-{4-[(methylamino)methyl]benzyl}azetidin-3-ol dihydrochloride (35 mg, 0.13 mmol) and DCM (5 mL).
Reaction SMILES: [C:1]1([CH3:28])[CH:6]=[CH:5][C:4]([NH:7][C:8]2[CH:16]=[C:15]([C:17]([OH:19])=O)[C:14]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=3)=[CH:13][C:9]=2[C:10](O)=[O:11])=[CH:3][CH:2]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O)CO>CN(C)C=O>[CH3:27][C:24]1[CH:23]=[CH:22][C:21]2[NH:20][C:14]3[C:15]([C:17](=[O:19])[C:26]=2[CH:25]=1)=[CH:16][C:8]1[NH:7][C:4]2[CH:3]=[CH:2][C:1]([CH3:28])=[CH:6][C:5]=2[C:10](=[O:11])[C:9]=1[CH:13]=3
Reactant: Cc1ccc(Nc2cc(C(=O)O)c(Nc3ccc(C)cc3)cc2C(=O)O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CN(C)C=O
Solvent: OCCO
Product: Cc1ccc2[nH]c3cc4c(=O)c5cc(C)ccc5[nH]c4cc3c(=O)c2c1
Temperature: 150 °C

Procedure:
A solution was prepared by mixing 2.0 g of 2,5-di-(p-toluidino)-terephthalic acid, 0.1 g of p-toluenesulfonic acid, 15 mL of ethylene glycol, and 20 mL of dimethylformamide. A fused silica glass capillary (equivalent diameter, 0.20 mm; and length, 4.0 m) was provided as a reactor, and was fixed in such a manner that a portion of 2.5 m length out of the whole capillary was immersed in an oil bath. The oil bath was heated to 150° C., and this solution was fed into the reactor at a flow velocity of 1.1 mL/hr (retention time: 5 minutes) with a syringe pump. A pigment having a vivid magenta color was obtained from the discharge port of the capillary.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]=1[CH3:14].CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.Br[CH:35]([C:37]1[CH:42]=[CH:41][C:40]([S:43]([CH3:46])(=[O:45])=[O:44])=[CH:39][CH:38]=1)[CH3:36].[I-].[Na+]>CN(C=O)C.C(OCC)(=O)C.CCOCC.O>[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH:35]([C:37]2[CH:38]=[CH:39][C:40]([S:43]([CH3:46])(=[O:44])=[O:45])=[CH:41][CH:42]=2)[CH3:36])[C:6]=1[CH3:14]
Reactant: COC(=O)Cc1c(C)[nH]c2ncccc12
Reactant: CC(Br)c1ccc(S(C)(=O)=O)cc1
Agent: CCN(CC)P1(=NC(C)(C)C)N(C)CCCN1C
Agent: [I-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CCOCC
Product: COC(=O)Cc1c(C)n(C(C)c2ccc(S(C)(=O)=O)cc2)c2ncccc12
Temperature: 25 °C
Reaction time: 0.58 h

Procedure:
A solution of (2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetic acid methyl ester ((2.37 g, 11.12 mmol) in dry DMF (38 ml) at room temperature is treated with BEMP (4.39 ml, 15.19 mmol) dropwise. The reaction mixture is stirred at room temperature for 35 minutes and then 1-(1-bromo-ethyl)-4-methanesulfonyl-benzene (4.00 g, 15.18 mmol) and sodium iodide (12.29 g, 15.28 mmol) is added. After stirring at 60° C. for 1 hour, the reaction mixture is allowed to cool to room temperature and then diluted with ethyl acetate/ether (200 ml of a 1:1 mixture) and water (150 ml). The organic portion is washed with brine, dried (Na2SO4) and concentrated in vacuo and the resulting crude is purified by chromatography on silica eluting with ethyl acetate/iso-hexane (2:3 increasing to 1:1 ethyl acetate) to yield the titled product as a racemic mixture. The enantiomers are resolved using a chiralcel OD column eluting with 30% IPA in hexanes to afford enantiomer A (retention time=14.33 minutes) and enantiomer B (retention time=17.68 minutes)
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([O:11][CH:12]([CH3:14])[CH3:13])[C:5]([CH3:10])=[C:6]([CH2:8][OH:9])[CH:7]=1>C(Cl)(Cl)Cl.O=[Mn]=O>[Br:1][C:2]1[CH:3]=[C:4]([O:11][CH:12]([CH3:14])[CH3:13])[C:5]([CH3:10])=[C:6]([CH:7]=1)[CH:8]=[O:9]
Reactant: Cc1c(CO)cc(Br)cc1OC(C)C
Agent: O=[Mn]=O
Solvent: ClC(Cl)Cl
Product: Cc1c(C=O)cc(Br)cc1OC(C)C
Temperature: 25 °C
Reaction time: 18 h
Yield: 72.5 %

Procedure:
To a solution of [5-bromo-2-methyl-3-(propan-2-yloxy)phenyl]methanol (108a, 25.0 g, 96.5 mmol) in CHCl3 (300 mL) was added MnO2 (42.0 g, 487 mmol). The mixture was stirred at room temperature for 18 hours. The mixture was filtered and the solids were washed with CH2Cl2 (2×20 mL). The filtrate was concentrated under vacuum to give 5-bromo-2-methyl-3-(propan-2-yloxy)benzaldehyde (108b, 18 g, 73%) as a colorless oil.
Reaction SMILES: C[O:2][C:3]([CH:5]1[C:14]2[N:13]=[CH:12][C:11]([CH3:15])=[CH:10][C:9]=2[CH2:8][CH2:7][CH2:6]1)=O.C([NH2:18])=O.C[O-].[Na+].CCCCCC>Cl>[CH3:15][C:11]1[CH:12]=[N:13][C:14]2[CH:5]([C:3]([NH2:18])=[O:2])[CH2:6][CH2:7][CH2:8][C:9]=2[CH:10]=1
Reactant: NC=O
Reactant: COC(=O)C1CCCc2cc(C)cnc21
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCCCCC
Product: Cc1cnc2c(c1)CCCC2C(N)=O
Reaction time: 1 h

Procedure:
A mixture of methyl-3-methyl-5,6,7,8-tetrahydroquinoline-8-carboxylate (25 g., 0.13 m), formamide (11.6, 0.26 m) and sodium methoxide (from 2.99 g., 0.13m sodium) was heated with stirring in an oil bath at 120° for 1 hour. The reaction mixture was further heated at 100° for 3 hours under reduced pressure (15 mm Hg). The cooled reaction mixture was diluted with 2N HCl to give an acidic solution which was extracted with ethylacetate (2 × 50 ml.) and the combined extracts discarded. The aqueous solution was adjusted to pH 9.0 with solid Na2CO3, saturated with NaCl and extracted with chloroform (3 × 100 ml.). The combined extracts were dried and evaporated to give a pale yellow oil which solidified on trituration with n-hexane. Recrystallisation from ethylacetate gave the title compound as colourless cubes (18.6 g., 88%) m.p. 110°. Found: C, 69.6; H, 7.4; N, 14.4%. C11H14N2O requires: C, 69.5; H, 7.4; N, 14.7%.
Reaction SMILES: [O:1]([CH2:19][CH:20]([CH3:35])[CH2:21][CH2:22][CH2:23][C:24]([CH:27]1[O:31][C:30]([CH2:33][Br:34])([OH:32])[CH2:29][CH2:28]1)([OH:26])[CH3:25])[Si:2]([C:15]([CH3:18])([CH3:17])[CH3:16])([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:36](OCC(C)CCCC(C1OC(CBr)(OC)CC1)(O)C)C1C=CC=CC=1>>[O:1]([CH2:19][CH:20]([CH3:35])[CH2:21][CH2:22][CH2:23][C:24]([CH:27]1[O:31][C:30]([CH2:33][Br:34])([O:32][CH3:36])[CH2:29][CH2:28]1)([OH:26])[CH3:25])[Si:2]([C:15]([CH3:18])([CH3:16])[CH3:17])([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CC(CCCC(C)(O)C1CCC(O)(CBr)O1)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Reactant: COC1(CBr)CCC(C(C)(O)CCCC(C)COCc2ccccc2)O1
Product: COC1(CBr)CCC(C(C)(O)CCCC(C)CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)O1

Procedure:
7-t-Butyldiphenylsiloxy-2-[2-bromomethyl-2-methoxy-tetrahydrofuran-5-yl]-6-methyl-heptan-2-ol is prepared as a mixture of cis:trans isomers by employing 7-t-butyldiphenylsiloxy-2-[2-bromomethyl-2-hydroxy-tetrahydrofuran-5-yl]-6-methyl-heptan-2-ol (1.33 g) in place of 7-benzyloxy-2-(2-bromomethyl-2-hydroxy-tetrahydrofuran-5-yl)-6-methyl-heptan-2-ol in the process for the preparation of 7-benzyloxy-2-[2-bromomethyl-2-methoxy-tetrahydrofuran-5-yl]-6-methyl-heptan-2-ol. The mixture of cis and trans isomers is separated by chromatography on silica gel (ethyl acetate:hexane gradient) to give the cis isomer as a yellow oil (0.324 g) and then the trans isomer as a yellow oil (0.151 g):
Reaction SMILES: C[Al](C)C.C1(C)C=CC=CC=1.C(N(CC)C(C)C)(C)C.[C:21](Br)(=[O:23])[CH3:22].[CH:25](=[O:30])[CH2:26][CH:27]([CH3:29])[CH3:28]>C(Cl)Cl.FC(F)(F)S(N[C@@H](C(C)C)CN(CC1C=CC=C(CN(C[C@H](C(C)C)NS(C(F)(F)F)(=O)=O)C[C@H](C(C)C)NS(C(F)(F)F)(=O)=O)C=1)C[C@H](C(C)C)NS(C(F)(F)F)(=O)=O)(=O)=O>[CH2:26]([C@@H:25]1[O:30][C:21](=[O:23])[CH2:22]1)[CH:27]([CH3:29])[CH3:28]
Reactant: CC(=O)Br
Reactant: CC(C)CC=O
Agent: CC(C)[C@@H](CN(Cc1cccc(CN(C[C@@H](NS(=O)(=O)C(F)(F)F)C(C)C)C[C@@H](NS(=O)(=O)C(F)(F)F)C(C)C)c1)C[C@@H](NS(=O)(=O)C(F)(F)F)C(C)C)NS(=O)(=O)C(F)(F)F
Agent: C[Al](C)C
Solvent: Cc1ccccc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)C[C@H]1CC(=O)O1
Temperature: 25 °C
Reaction time: 3 h
Yield: 78 %

Procedure:
In an atmosphere of argon, the ligand (6) obtained in Example 6 (0.10 g, 0.10 mmol) was suspended in methylene chloride (5 ml) in a Schlenk glassware, and to this suspension was added trimethylaluminum in toluene (0.20 ml of 1M solution, 0.20 mmol) via a syringe. Then, the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture changed from a white suspension into a colorless solution. After completion of the stirring, the solvent was removed by evaporation under reduced pressure. Hexane (5 ml) was added to the residue, and the mixture was further stirred for one hour. After that, the mixture was allowed to stand for a while, and the supernatant liquid was removed by means of a syringe. The precipitate was dried under reduced pressure to give a catalyst. To the catalyst obtained was added methylene chloride (16 ml), followed by the addition of N,N-diisopropylethylamine (0.59 ml, 3.4 mmol). The mixture was cooled to −78° C. in a dry ice-ethanol bath. To this were added acetyl bromide (0.28 ml, 3.8 mmol) and isovaleraldehyde (0.21 ml, 2.0 mmol) via a syringe, and the mixture was stirred at −50° C. for 24 hours, during which time the reaction solution turned pale yellow. After completion of the reaction, the reaction mixture changed to orange when it was warmed up to room temperature. The reaction mixture was filtered through a glass filter packed with silica gel, and the solvent of the filtrate was evaporated off to give (S)-4-isobutyl-2-oxetanone (0.20 g, 77% yield). The asymmetric yield of the product was measured by means of GLC using a capillary column Chirasil-DEX CB (0.25 mm×25 m, membrane thickness 0.25 μm, GL Science) and was found to be 93% e.e.
Reaction SMILES: [P:1]([O-:6])([O:4][CH3:5])[O:2][CH3:3].[CH3:7]/[C:8](/[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[CH:9]\[CH:10]=[O:11].Cl>>[OH:11][C@@H:10]([P:1](=[O:6])([O:4][CH3:5])[O:2][CH3:3])/[CH:9]=[C:8](\[CH3:7])/[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: C/C(=C\C=O)c1ccccc1
Reactant: COP([O-])OC
Agent: Cl
Product: COP(=O)(OC)[C@H](O)/C=C(\C)c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 93 %

Procedure:
The solution of ALB in tetrahydrofuran (0.1 M, 0.40 ml) obtained in Example 1 was concentrated at room temperature for 1 hour under reduced pressure, then 0.4 ml of toluene was added thereto under an argon atmosphere. To this solution was added dimethyl phosphite (37 μl, 0.40 mmol) at room temperature. After stirring at room temperature for 30 minutes, the reaction vessel was cooled to -40° C., and it was maintained at this temperature for 15 minutes, then (E)-β-methylcinnamaldehyde (0.40 mmol) was added thereto. After reacting for 81 hours, 1N hydrochloric acid was added thereto to stop the reaction. The mixture was extracted with ethyl acetate (10 ml×three times), and the combined extracts were washed with brine and dried over Na2SO4. The solvent was distilled, and the residue was purified by flash column chromatography (acetone/hexane=1/5, on SiO2) to obtain dimethyl (S,E)-1-hydroxy-3-methyl-3-phenyl-2-propenylphosphonate as a final product in a yield of 93%. The chemical reaction in this Example is shown in chemical formula 35. ##STR29##
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[Al+3].[Cl-].[Cl-].[Cl-].[CH3:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([CH3:18])=[C:15]([OH:17])[CH:16]=1>ClCCCl.CO.C1COCC1.[Li+].[OH-]>[OH:17][C:15]1[C:14]([CH3:18])=[CH:13][C:12]([C:1](=[O:3])[CH3:2])=[C:11]([O:10][CH3:9])[CH:16]=1
Reactant: COc1ccc(C)c(O)c1
Reactant: CC(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Agent: [Li+]
Solvent: ClCCCl
Solvent: CO
Solvent: C1CCOC1
Product: COc1cc(O)c(C)cc1C(C)=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 29.9 %

Procedure:
1.16 ml (16 mmol) Acetylchloride were added within 5 min to a ice cooled suspension of 2.4 g (16.4 mmol) AlCl3 in 5 ml 1,2-dichloroethane under an argon atmosphere. A solution of 1.13 g (8.2 mmol) 5-methoxy-2-methyl-phenol (PCT Int. Appl. WO 2003/084916 A2) in 2.4 ml 1,2-dichloroethane was added within 5 min. The mixture was naturally warmed to ambient temperature, poured after 4 h onto ice water and extracted twice with dichloromethane. The combined extracts were washed with ice water/0.5 M NaOH solution 1/1 and brine and dried over sodium sulfate. Removal of the solvent under reduced pressure gave a yellow oil which was dissolved in a mixture of 3.5 ml methanol, 7 ml THF and 7 ml 1 M LiOH solution. The solution was stirred for 30 min at ambient temperature and the solvent was partially removed under reduced pressure. Ice water/1 M HCl solution 1/1 was added and the solution was extracted twice with ethyl acetate. The combined extracts were washed with brine and dried over sodium sulfate. Evaporation of the solvent left a yellow solid which was crystallized from dichloromethane/methanol/heptane to yield 441 mg (2.45 mmol, 30%) of the title compound as colorless crystals.
Reaction SMILES: [OH:1][C:2]1[C:11]([N+:12]([O-])=O)=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([C:15]([F:18])([F:17])[F:16])[CH:3]=1>CO.[C].[Pd]>[NH2:12][C:11]1[C:2]([OH:1])=[CH:3][C:4]([C:15]([F:16])([F:17])[F:18])=[C:5]([CH:10]=1)[C:6]([O:8][CH3:9])=[O:7]
Reactant: COC(=O)c1cc([N+](=O)[O-])c(O)cc1C(F)(F)F
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1cc(N)c(O)cc1C(F)(F)F
Temperature: 25 °C
Reaction time: 8 h
Yield: 103 %

Procedure:
Methyl 4-hydroxy-5-nitro-2-(trifluoromethyl)benzoate (58.0 g) was dissolved in methanol (600 ml), and thereto was added 10% palladium carbon (50% wet.: 11.60 g). The mixture was vigorously stirred under hydrogen atmosphere at 25° C. for 8 hours. After the reaction was complete, the mixture was filtered on celite, washed with methanol, and the filtrate was concentrated under reduced pressure to give the title compound (53.0 g).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[CH:3]=1.[C:9]([N:13]1[CH:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:16]([CH3:24])[N:15]([CH3:25])[C:14]1=[O:26])(=[O:12])[CH:10]=[CH2:11].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.CCN(C(C)C)C(C)C>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:25][N:15]1[CH:16]([CH3:24])[CH:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:13]([C:9](=[O:12])/[CH:10]=[CH:11]/[C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[CH:3]=2)[C:14]1=[O:26]
Reactant: Fc1cccc(Br)c1
Reactant: C=CC(=O)N1C(=O)N(C)C(C)C1c1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC1C(c2ccccc2)N(C(=O)/C=C/c2cccc(F)c2)C(=O)N1C
Temperature: 110 °C
Yield: 76 %

Procedure:
A solution of 1-bromo-3-fluorobenzene (525 mg, 3 mmole), (4 R, 5 S)-1-acryloyl-3,4-dimethyl-5-phenylimidazolidin-2-one (500 mg, 2 mmole), Pd(OAc)2 (22 mg, 0.10 mmole), P(o-tolyl)3 (61 mg, 0.20 mmole), and (i-Pr)2NEt (0.73 mL, 4.2 mmole) in dry DMF (10 mL) was degassed (3×vacuum/N2 purge) then heated to 110° C. After 2 hr the mixture was cooled and poured into EtOAc. The resulting mixture was washed with H2O (3×), and the combined aqueous layers were back-extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered through a plug of silica gel, and concentrated. The residue was taken up in 1:1 Et2O/hexanes (10 mL) and cooled at −20° C. overnight. The solid was collected and dried in vacuo to afford the title compound (514 mg, 76%): 1H NMR (300 MHz, CDCl3) δ 8.18 (d, J=15.9 Hz, 1 H), 7.64 (d, J=15.9 Hz, 1 H), 7.15-7.45 (m, 8 H), 6.98-7.10 (m, 1 H), 5.42 (d, J=8.5 Hz, 1 H), 3.88-4.03 (m, 1 H), 2.88 (s, 3 H), 0.85 (d, J=6.6 Hz, 3 H); MS (ES) m/e 339 (M+H)+.
Reaction SMILES: C([O:8][C:9]1[C:14]([CH3:15])=[CH:13][C:12]([O:16][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:11][C:10]=1[Cl:25])C1C=CC=CC=1.[H][H]>[C].[Pd].C(OCC)(=O)C>[C:17]([O:16][C:12]1[CH:13]=[C:14]([CH3:15])[C:9]([OH:8])=[C:10]([Cl:25])[CH:11]=1)(=[O:24])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: Cc1cc(OC(=O)c2ccccc2)cc(Cl)c1OCc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: Cc1cc(OC(=O)c2ccccc2)cc(Cl)c1O
Temperature: 25 °C
Reaction time: 10 h
Yield: 95.9 %

Procedure:
A reaction vessel was charged with 35 g of 4-benzyloxy-3-chloro-5-methyl-1-benzoyloxybenzene and 200 ml of ethyl acetate, and the air in the vessel was replaced with nitrogen. Then, 2 g of 10% palladium carbon was added, and the nitrogen in the vessel was replaced with hydrogen, followed by vigorous stirring at room temperature for 10 hours. The hydrogen in the vessel was replaced with nitrogen, after which the reaction mixture was filtered, and the filtrate was concentrated. The residue was subjected to silica gel chromatography, which afforded 25 g of 4-benzoyloxy-2-chloro-6-methylphenol (96% yield).