Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][NH2:11])=[CH:6][CH:5]=1.CO[CH:14](OC)[CH2:15][C:16](=O)[CH3:17].C(=O)([O-])[O-].[K+].[K+]>C(O)C>[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[CH:15][C:16]([CH3:17])=[N:11]2)=[CH:6][CH:5]=1
Reactant: COc1ccc(NN)cc1
Reactant: COC(CC(C)=O)OC
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: COc1ccc(-n2ccc(C)n2)cc1

Procedure:
A mixture of 17 parts of (4-methoxyphenyl)hydrazine hydrochloride, 14 parts of 4,4-dimethoxy-2-butanone, 14 parts of potassium carbonate and 240 parts of ethanol is stirred and refluxed for 2 hours. The reaction mixture is evaporated and the residue is stirred and refluxed for 1 hour with 200 parts of hydrochloric acid solution 10%. The solvent is evaporated and the residue is neutralized with ammonium hydroxide. The product is extracted three times with 2,2'-oxybispropane. The combined extracts are washed with water, dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using trichloromethane as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from hexane. The product is filtered off and dried, yielding 2.4 parts of 1-(4-methoxyphenyl)-3-methyl-1H-pyrazole.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:13](=[O:14])[C:12]([C:15]([O:17]CC)=[O:16])=[CH:11][N:10]1[CH3:20].O1CCCC1.[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:13](=[O:14])[C:12]([C:15]([OH:17])=[O:16])=[CH:11][N:10]1[CH3:20]
Reactant: CCOC(=O)c1cn(C)n(-c2c(Cl)cccc2Cl)c1=O
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: Cn1cc(C(=O)O)c(=O)n1-c1c(Cl)cccc1Cl
Yield: 88.7 %

Procedure:
In the same manner as in Reference Example 65 and using ethyl 2-(2,6-dichlorophenyl)-1-methyl-3-oxo-2,3-dihydro-1H-pyrazole-4-carboxylate (3.4 g, 11 mmol), tetrahydrofuran (6 mL), methanol (5 mL) and 4N aqueous sodium hydroxide solution (8 mL) as starting materials, the title compound (2.8 g, 90%) was obtained as a white solid.
Reaction SMILES: N1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2N=N1.Cl[C:11]1[CH:27]=[CH:26][C:14]2=[N:15][N:16]([C:18]3[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][C:19]=3[OH:25])[N:17]=[C:13]2[CH:12]=1>>[OH:25][C:19]1[C:20]([CH2:8][CH2:9][CH2:4][CH2:5][CH2:6][CH2:7][CH2:4][CH2:9][CH2:8][CH2:7][CH2:6][CH3:5])=[CH:21][C:22]([CH3:24])=[CH:23][C:18]=1[N:16]1[N:17]=[C:13]2[CH:12]=[CH:11][CH:27]=[CH:26][C:14]2=[N:15]1
Reactant: Cc1ccc(O)c(-n2nc3ccc(Cl)cc3n2)c1
Reactant: c1ccc2[nH]nnc2c1
Product: CCCCCCCCCCCCc1cc(C)cc(-n2nc3ccccc3n2)c1O

Procedure:
In like manner, 5-chloro-2-(2-hydroxy-3-dodecyl-5-methylphenyl-2H-benzotriazole is prepared by substituting for the benzotriazole used above an equivalent amount of 5-chloro-2-(2-hydroxy-5-methylphenyl)-2H-benzotriazole.
Reaction SMILES: [CH2:1]([NH:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[Cl:11])[CH3:2].Br[C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][CH:15]=1>>[Cl:11][C:6]1[CH:7]=[CH:8][CH:9]=[C:10]([C:22]2[C:23]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:19]=[CH:20][CH:21]=2)[C:5]=1[C:4]([NH:3][CH2:1][CH3:2])=[O:12]
Reactant: Brc1cccc2ccccc12
Reactant: CCNC(=O)c1ccccc1Cl
Product: CCNC(=O)c1c(Cl)cccc1-c1cccc2ccccc12
Yield: 28 %

Procedure:
The title compound was prepared from the compound of Example f and 1-bromonaphthalene (0.76 g, 3.65 mmol) according to General Method D. It was obtained as 0.28 g of a white solid, a 28% yield. m.p. 181°-182° C.
Reaction SMILES: [CH3:1][CH2:2][O:3][C:4]([CH:6]1[C:11](=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5].Cl>C(OCC)C>[OH:12][CH:11]1[CH2:10][CH2:9][CH2:8][CH2:7][CH:6]1[C:4]([O:3][CH2:2][CH3:1])=[O:5]
Reactant: CCOC(=O)C1CCCCC1=O
Agent: Cl
Solvent: CCOCC
Product: CCOC(=O)C1CCCCC1O
Temperature: 25 °C
Reaction time: 8 h
Yield: 78.4 %

Procedure:
3.2 g of borane/tert-butylamine complex was added to 200 ml of diethyl ether solution containing 17.0 g (0.10 mol) of ethyl cyclohexanone-2-carboxylate and stirred overnight at room temperature. An aqueous diluted hydrochloric acid was added thereto to make it weakly acidic, which was then subjected to liquid-liquid separation. The organic layer thus separated was dried, concentrated and then distilled under reduced pressure to obtain 13.5 g of ethyl 2-hydroxycyclohexanecarboxylate. Yield: 78.5%. b.p. 68° to 71° C. (0.2 mmHg).
Reaction SMILES: FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([C:17]2([C:34]([F:37])([F:36])[F:35])[O:21][N:20]=[C:19]([C:22]3[CH:23]=[C:24]4[C:28](=[CH:29][CH:30]=3)[C:27]3([CH2:33][NH:32][CH2:31]3)[O:26][CH2:25]4)[O:18]2)[CH:12]=[C:13]([Cl:16])[C:14]=1[F:15].C(N(CC)CC)C.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[CH3:67][S:68]([CH2:71][C:72](O)=[O:73])(=[O:70])=[O:69]>CN(C=O)C>[Cl:8][C:9]1[CH:10]=[C:11]([C:17]2([C:34]([F:36])([F:37])[F:35])[O:21][N:20]=[C:19]([C:22]3[CH:23]=[C:24]4[C:28](=[CH:29][CH:30]=3)[C:27]3([CH2:33][N:32]([C:72](=[O:73])[CH2:71][S:68]([CH3:67])(=[O:70])=[O:69])[CH2:31]3)[O:26][CH2:25]4)[O:18]2)[CH:12]=[C:13]([Cl:16])[C:14]=1[F:15]
Reactant: CS(=O)(=O)CC(=O)O
Reactant: Fc1c(Cl)cc(C2(C(F)(F)F)ON=C(c3ccc4c(c3)COC43CNC3)O2)cc1Cl
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O=C(O)C(F)(F)F
Product: CS(=O)(=O)CC(=O)N1CC2(C1)OCc1cc(C3=NOC(c4cc(Cl)c(F)c(Cl)c4)(C(F)(F)F)O3)ccc12
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a stirred solution of trifluoroacetic acid salt of 5′-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-1,4,2-dioxazol-3-yl)-3′H-spiro[azetidine-3,1′-isobenzofuran](Preparation 45, 0.3 g, 0.648 mmol, 1 eq) in DMF (5 mL) was added triethyl amine (0.727 mL, 5.181mmol, 8 eq), followed by addition of EDC.HCl (0.185 g, 0.971 mmol, 1.5 eq), HOBt (0.087 g, 0.648 mmol, 1 eq) and methane sulfonyl acetic acid (0.178 g, 1.295 mmol, 2 eq) at room temperature. Resulting reaction mixture was stirred at room temperature for 18 hours under nitrogen atmosphere. After complete consumption of starting material, reaction mixture was quenched by water (50 mL) and extracted with ethyl acetate (3×30 mL). Combined organic phase was washed with saturated solution of LiCl solution (30 mL), brine (30 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to get brown thick oil (0.48 g, crude). Crude was purified by combiflash using 40 g Redisep column. Desired compound was eluted in 52% ethyl acetate in hexane to afford title compound as off white solid (0.228 g, 60.35%). 1H NMR (400 MHz, CDCl3) δ: 3.19 (s, 3H), 3.86 (s, 2H), 4.35 (d, J=11.16 Hz, 1H), 4.45 (d, J=11.16 Hz, 1H), 4.67 (t, J=10.72 Hz, 2H), 5.19 (s, 2H), 7.63-7.66 (m, 3H), 7.70 (s, 1H), 7.89 (d, J=8.08 Hz, 1H). (m/z): 580.9 (M−H), HPLC Purity: 95.78%.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8]([CH3:10])[CH:7]=[CH:6][C:5]=1[I:11](Cl)Cl)([O-:3])=[O:2].[OH-:14].[Na+]>>[N+:1]([C:4]1[CH:9]=[C:8]([CH3:10])[CH:7]=[CH:6][C:5]=1[I:11]=[O:14])([O-:3])=[O:2]
Reactant: Cc1ccc(I(Cl)Cl)c([N+](=O)[O-])c1
Reactant: [OH-]
Agent: [Na+]
Product: Cc1ccc(I=O)c([N+](=O)[O-])c1
Reaction time: 0.25 h

Procedure:
2-Nitro-4-methyl(dichloroiodo)benzene (2.0 g, 6.0 mmol) was added portion-wise, over a period of 15 min, to a cold (5° C.), stirred solution of 20 percent aqueous sodium hydroxide (100 mL). Five min after the addition, the desired product, an orange solid, insoluble in the reaction medium, was isolated by filtration; yield, 1.51. g.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11]2)=[C:6]([CH:9]=1)[C:7]#[N:8].[CH3:16][O:17][C:18]1[CH:30]=[CH:29][C:21]([CH2:22][N:23]2[CH:27]=[N:26][C:25]([NH2:28])=[N:24]2)=[CH:20][CH:19]=1>>[CH3:16][O:17][C:18]1[CH:19]=[CH:20][C:21]([CH2:22][N:23]2[CH:27]=[N:26][C:25]([NH:28][C:2]3[CH:3]=[CH:4][C:5]([N:10]4[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11]4)=[C:6]([CH:9]=3)[C:7]#[N:8])=[N:24]2)=[CH:29][CH:30]=1
Reactant: Cc1cn(-c2ccc(Br)cc2C#N)cn1
Reactant: COc1ccc(Cn2cnc(N)n2)cc1
Product: COc1ccc(Cn2cnc(Nc3ccc(-n4cnc(C)c4)c(C#N)c3)n2)cc1

Procedure:
Prepared in analogy to example 1b) starting with 5-bromo-2-(4-methyl-imidazol-1-yl)-benzonitrile and 1-(4-methoxy-benzyl)-1H-[1,2,4]triazol-3-ylamine. The title compound was obtained as a colorless oil (Yield=34%). MS ISP (m/e): 386.2 (100) [(M+H)+].
Reaction SMILES: [C:1]([CH2:3][C@@H:4]1[CH2:12][C@@H:11]2[C@@H:7]([CH2:8][N:9]([C:13](=[O:29])[CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[O:21]CC3C=CC=CC=3)[CH2:10]2)[C@@:6]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[O:37][CH3:38])([OH:30])[CH2:5]1)#[N:2].[H][H]>[OH-].[OH-].[Pd+2].C(O)C>[C:1]([CH2:3][C@@H:4]1[CH2:12][C@@H:11]2[C@@H:7]([CH2:8][N:9]([C:13](=[O:29])[CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[OH:21])[CH2:10]2)[C@@:6]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[O:37][CH3:38])([OH:30])[CH2:5]1)#[N:2]
Reactant: COc1ccccc1[C@]1(O)C[C@H](CC#N)C[C@H]2CN(C(=O)Cc3ccccc3OCc3ccccc3)C[C@H]21
Reactant: [H][H]
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCO
Product: COc1ccccc1[C@]1(O)C[C@H](CC#N)C[C@H]2CN(C(=O)Cc3ccccc3O)C[C@H]21
Yield: 56 %

Procedure:
(3aS,4S,6S,7aR)-6-Cyanomethyl-2-[(2-hydroxyphenyl)acetyl]-4-(2-methoxyphenyl)perhydroisoindol-4-ol is obtained by proceeding as described in Example 4, from 1.3 g of (3aS,4S,6S,7aR)-6-cyanomethyl-2-[(2-benzyloxyphenyl)acetyl]-4-(2-methoxyphenyl)perhydroisoindol-4-ol, 130 cm3 of ethanol, 0.3 g of 20% palladium hydroxide on carbon black, and hydrogen. Purification by chromatography gives 0.60 g of (3aS,4S,6S,7aR)-6-cyanomethyl-2-[(2-hydroxyphenyl)acetyl]-4-(2-methoxyphenyl)perhydroisoindol-4-ol in the form of a thick white foam.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH:11]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)[C:12]([OH:14])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[N:51]1([C:57]2[C:66]3[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=3)[N:60]=[CH:59][N:58]=2)[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][CH2:10][CH:11]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)[C:12](=[O:14])[N:54]1[CH2:55][CH2:56][N:51]([C:57]2[C:66]3[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=3)[N:60]=[CH:59][N:58]=2)[CH2:52][CH2:53]1)([CH3:2])([CH3:3])[CH3:4]
Reactant: Cc1ccc(CC(CCNC(=O)OC(C)(C)C)C(=O)O)cc1
Reactant: c1ccc2c(N3CCNCC3)ncnc2c1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN1CCOCC1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1ccc(CC(CCNC(=O)OC(C)(C)C)C(=O)N2CCN(c3ncnc4ccccc34)CC2)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 58 %

Procedure:
To a solution containing 4-tert-Butoxycarbonylamino-2-(4-methylbenzyl)-butyric acid (0.24 g, 0.77 mmol) in 25 mL of DMF under a nitrogen atmosphere was added EDCI (0.16 g, 0.84 mmol), HOBT (130 mg, 0.84 mmol) and NMM (0.28 g, 2.8 mmol.) After stirring at room temperature for 15 minutes, 4-Piperazin-1-yl-quinazoline (200 mg, 0.93 mmol) was added and the reaction allowed to stir at room temperature. The reaction was diluted with ethyl acetate and washed with water, saturated sodium bicarbonate and water. The organic phase was dried over magnesium sulfate. Filtration, removal of solvent and purification of the residue via biotage eluting with 10% MeOH/DCM gave [3-(4-Methyl-benzyl)-4-oxo-4-(4-quinazolin-4-yl-piperazin-1-yl)-butyl]-carbamic acid tert-butyl ester (0.225 g, 64%) as a white solid. LCMS (APCI+) m/z 504 [M+H]+; Rt: 3.03 min. 1H NMR (CDCl3, 400 MHz) δ 3.8.69 (1H, s), 7.92 (1H, d, J 8.3 Hz), 7.76-7.71 (2H, m), 7.45 (1H, t, J 7.8 Hz), 7.06 (4H, m), 4.53 (1H, br. s), 3.96-3.76 (2H, m), 3.63-3.54 (2H, m), 3.47-3.40 (2H, m), 3.24-2.84 (6H, m), 2.76-2.70 (1H, m), 2.27 (3H, s), 2.09-2.00 (1H, m), 1.73-1.65 (1H, m), 1.40 (9H, s.)
Reaction SMILES: [OH:1][C:2]1([C:16]([O:18][CH3:19])=[O:17])[CH2:11][CH2:10][C:9]2[C:4](=[C:5]([O:14][CH3:15])[CH:6]=[CH:7][C:8]=2[O:12][CH3:13])[CH2:3]1.[C:20](OC(=O)C)(=[O:22])[CH3:21].O>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[C:20]([O:1][C:2]1([C:16]([O:18][CH3:19])=[O:17])[CH2:11][CH2:10][C:9]2[C:4](=[C:5]([O:14][CH3:15])[CH:6]=[CH:7][C:8]=2[O:12][CH3:13])[CH2:3]1)(=[O:22])[CH3:21]
Reactant: COC(=O)C1(O)CCc2c(OC)ccc(OC)c2C1
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Solvent: O
Solvent: c1ccncc1
Product: COC(=O)C1(OC(C)=O)CCc2c(OC)ccc(OC)c2C1
Temperature: 0 °C
Reaction time: 24 h
Yield: 96.5 %

Procedure:
5.0 g of methyl rac-1,2,3,4-tetrahydro-2-hydroxy-5,8-dimethoxynaphthalene-2-carboxylate were dissolved in 50 ml of pyridine. The solution was cooled to 0° C. and 10 ml of acetic anhydride and 150 mg of 4-dimethylaminopyridine were added. After standing at 0° C. for 24 hours, the mixture was poured into 250 ml of water. The mixture obtained was extracted with three 100 ml portions of ethyl acetate and the combined ethyl acetate extracts were washed with 2-N hydrochloric acid until the washings were acidic, then with 200 ml of water, 200 ml of dilute aqueous potassium hydrogen carbonate and 200 ml of brine. After drying, the solvent was evaporated to give a white crystalline residue. Recrystallisation from diethyl ether gave 5.6 g (96.5%) of methyl rac-2-acetoxy-1,2,3,4-tetrahydro-5,8-dimethoxynaphthalene-2-carboxylate in the form of colourless crystals of melting point 155.5°-156° C.
Reaction SMILES: [CH2:1]([N:3]1[C:11]2[C:6](=[C:7]([CH2:12][N:13]([CH3:18])[C:14](=[O:17])[CH:15]=[CH2:16])[CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4]1)[CH3:2].CN(CC1SC2C=CC=CC=2C=1C)C(=O)C=C.Br[C:37]1[CH:38]=[C:39]2[C:44](=[N:45][CH:46]=1)[NH:43][C:42](=[O:47])[CH2:41][CH2:40]2.BrC1C=NC2NC(=O)C(C)(C)NCC=2C=1>>[CH2:1]([N:3]1[C:11]2[C:6](=[C:7]([CH2:12][N:13]([CH3:18])[C:14](=[O:17])/[CH:15]=[CH:16]/[C:37]3[CH:46]=[N:45][C:44]4[NH:43][C:42](=[O:47])[CH2:41][CH2:40][C:39]=4[CH:38]=3)[CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4]1)[CH3:2]
Reactant: O=C1CCc2cc(Br)cnc2N1
Reactant: C=CC(=O)N(C)Cc1cccc2c1ccn2CC
Agent: C=CC(=O)N(C)Cc1sc2ccccc2c1C
Agent: CC1(C)NCc2cc(Br)cnc2NC1=O
Product: CCn1ccc2c(CN(C)C(=O)/C=C/c3cnc4c(c3)CCC(=O)N4)cccc21
Yield: 46 %

Procedure:
The title compound was prepared according to the procedure of Example 2, except substituting (N-((1-ethyl-1H-indol-4-yl)methyl)-N-methylacrylamide) for N-methyl-N-(3-methyl-benzo[b]thiophen-2-ylmethyl)acrylamide and 6-bromo-3,4-dihydro-1,8-naphthyridin-2(1H)-one for 7-bromo-3,3-dimethyl-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one. The title compound (329 mg, 46%) was obtained as an off-white solid and a mixture of amide rotomers: 1H NMR (400 MHz, DMSO-d6) δ 10.62-10.58 (m, 1H), 8.38-7.98 (m, 2H), 7.57-7.53 (m, 1H), 7.42-7.08 (m, 4H), 6.92-6.78 (m, 1H), 6.51 (s, 1H), 5.05-4.88 (m, 2H), 4.22-4.19 (m, 2H), 3.04-2.85 (m, 5H), 2.55-2.50 (m, 2H), 1.35 (t, J=7.2 Hz, 3H); ESI MS m/z 389 [C23H24N4O2+H]+.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:13]=[CH:12][C:9]([CH:10]=O)=[CH:8][CH:7]=1.[CH3:14][C:15]([C:17]([CH3:20])([CH3:19])[CH3:18])=[O:16]>C(O)C.O.[OH-].[Na+]>[CH3:18][C:17]([CH3:20])([CH3:19])[C:15](=[O:16])[CH:14]=[CH:10][C:9]1[CH:12]=[CH:13][C:6]([CH:2]2[O:3][CH2:4][CH2:5][O:1]2)=[CH:7][CH:8]=1
Reactant: O=Cc1ccc(C2OCCO2)cc1
Reactant: CC(=O)C(C)(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CC(C)(C)C(=O)C=Cc1ccc(C2OCCO2)cc1
Reaction time: 1 h
Yield: 38.8 %

Procedure:
100 g (0.5612 mol) of 4-(1,3-dioxolan-2-yl)-benzaldehyde and 56.1 g (0.56 mol) of pinacoline are dissolved in a mixture of 280 ml of ethanol and 56 ml of water, and 17 ml of 10% strength sodium hydroxide solution are added at room temperature. The mixture is subsequently stirred for 1 hour, 0.56 g of solid sodium hydroxide are added and the mixture is subsequently stirred for 2 days. Thereafter, the precipitate is filtered off with suction, washed with 200 ml of ethanol/water (1:1) and then with water, dried and recrystallized twice from ethanol. 56.5 g (39% of theory) of 4,4-dimethyl-1-[4-(1,3-dioxolan-2-yl)-phenyl]-1-penten-3-one of melting point 79°-81° C. are obtained.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:12]=[CH:13][C:14]3[O:23][C:22]4[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][C:17]=4[C:15]=3[CH:16]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:12]=[CH:13][C:14]3[O:23][C:22]4[CH2:21][CH2:20][NH:19][CH2:18][C:17]=4[C:15]=3[CH:16]=2)(=[O:9])=[O:10])=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCc2oc3ccc(S(=O)(=O)c4ccc(F)cc4)cc3c2C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=S(=O)(c1ccc(F)cc1)c1ccc2oc3c(c2c1)CNCC3
Temperature: 25 °C
Reaction time: 2 h
Yield: 58.4 %

Procedure:
To the product obtained in step A (150 mg, 0.31 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (0.6 mL). After stirring for 2 h at ambient temperature the reaction mixture was quenched with 10% sodium bicarbonate solution (20 mL) and extracted with dichloromethane. The organic extract was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, 90:10 dichloromethane/methanol) to give 8-(4-fluorophenylsulfonyl)-1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine (60 mg, 52%) as a white solid: 1H NMR (CDCl3, 300 MHz) δ 8.03 (d, J=1.8 Hz, 1H), 8.00-7.92 (m, 2H), 7.78 (dd, J=8.7, 2.1 Hz, 1H), 7.51 (d, J=9.0 Hz, 1H), 7.21-7.10 (m, 2H), 4.00 (t, J=2.1 Hz, 2H), 3.25 (t, J=5.7 Hz, 2H), 2.84-2.76 (m, 2H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:15](=[O:16])[CH:14]2[CH:9]1[CH:10]1[CH2:17][CH:13]2[CH:12]=[CH:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:18]1CCCC1.[OH-].[Li+].Cl>O.C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][CH:9]1[CH:10]2[CH2:17][CH:13]([CH:12]=[CH:11]2)[CH:14]1[C:15]([OH:18])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C1CCOC1
Reactant: CC(C)(C)OC(=O)N1C(=O)C2C3C=CC(C3)C21
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: CC(C)(C)OC(=O)NC1C2C=CC(C2)C1C(=O)O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Combine 4-Oxo-3-aza-tricyclo[4.2.1.0(2,5)]non-7-ene-3-carboxylic acid tert-butyl ester (60.94 g, 0.2590 mol) and Tetrahydrofuran (800 mL, 10 mol) in 2 L Erlenmeyer flask. Addition of 1.00 M of Lithium hydroxide in Water (780 mL) gave a slight exotherm and the flask was cooled during addition of LiOH solution with an ice water bath. The mixture was then warmed to rt following addition and stirred at room temperature overnight. Cooled 0° C. in ice/water bath. Added conc HCl to pH 2. A milky white liquid ensued. The THF was mostly removed by rotovap to give a precipitated solid in the water. This aqueous/solid mixture was diluted with 700 mL of CH2Cl2 and stirred for two hours during which the solid completely dissolved in the organic layer. The aqueous was further extracted with 400 mL of CH2Cl2 and the combined organics were dried (MgSO4), filtered and concentrated to give 3-tert-Butoxycarbonylamino-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid as an off-white solid, put on high vac at 40° C. to remove excess dichloromethane present in the solid sample. (60.40 g, 92%). 1H-NMR (CDCL3, 400 MHz): δ 12.0 (broad absorption, 1H) 6.97 (d, J=10.6 Hz, 1H), 6.20 (s, 1H); 3.96 (t, J=9.6 Hz, 1H), 2.99 (s, 1H), 2.74 (s, 1H), 2.60 (d, J=8.4 Hz, 1H), 2.09 (d, J=9.3 Hz, 1H), 1.66 (d, J=9.4 Hz, 1H), 1.47 (s, 9H).
Reaction SMILES: [CH3:1][O:2][CH:3]([O:9][CH3:10])[C:4]([CH3:8])([CH3:7])[CH2:5][OH:6].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>C(Cl)Cl>[CH3:1][O:2][CH:3]([O:9][CH3:10])[C:4]([CH3:8])([CH3:7])[CH:5]=[O:6]
Reactant: COC(OC)C(C)(C)CO
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: COC(OC)C(C)(C)C=O

Procedure:
A suspension of 90 g (0.61mol) of the product of Example 2 and 250mg (0.66 mol) of pyridinium dichromate was stirred rapidly in 2 L of CH2Cl2 for 40 hours. The mixture was filtered through Celite, the filtrate passed through a column of Florisil and the solvent evaporated. Distillation of the residue through a 45 cm vigreux column furnished the title compound as a water-white oil, bp 65°-68°/10 mm, 31.4 g (35%). Calculated for C7H14O3 : C,57.51; H, 9.65. Found: C, 57.69; H, 9.85.
Reaction SMILES: C([O:24][CH:25]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[CH3:26])(=O)CCCCCCCCCCCCCCCCCCCCC>O>[CH3:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][C@@H:25]([OH:24])[CH3:26]
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)OC(C)CCCCCC
Solvent: O
Product: CCCCCC[C@H](C)O
Yield: 34 %

Procedure:
Interesterification was carried out by using 3 g of Lipase QL, 50 g of (R,S)-2-octanol, and 150 g of tribehen under the same conditions as in Example 3 at 120° C. for a period of 22 hours. The water content of the reaction system was 0.03% by weight, and 91% of the lipase particles had a particle size of 20 to 40 μm. Gas chromatography of the reaction mixture revealed that 64 mol % of (R,S)-2-octanol had been converted to 2-octyl behenate. The reaction mixture was treated in the same manner as in Example 3 and subjected to simple distillation at 65° C. and 5 mmHg to give (S)-(+)-octanol (yield: 34%; chemical purity: 99.9%; optical purity: 98.2% ee). On the other hand, the residue, i.e., (R)-(-)-2-octyl behenate was alkali-hydrolyzed in the same manner as in Example 1 to obtain (R)-(-)-2-octanol (yield: 85%; chemical purity: 99.6%; optical purity: 62% ee).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([N:9]2[C:13]([CH3:14])=[CH:12][C:11]([CH3:15])=[N:10]2)[N:3]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][CH:18]=1.Cl>O.C(O)C>[Cl:8][C:6]1[N:5]=[C:4]([N:9]2[C:13]([CH3:14])=[CH:12][C:11]([CH3:15])=[N:10]2)[N:3]=[C:2]([NH:21][C:20]2[CH:22]=[CH:23][C:17]([Cl:16])=[CH:18][CH:19]=2)[CH:7]=1
Reactant: Nc1ccc(Cl)cc1
Reactant: Cc1cc(C)n(-c2nc(Cl)cc(Cl)n2)n1
Agent: Cl
Solvent: CCO
Solvent: O
Product: Cc1cc(C)n(-c2nc(Cl)cc(Nc3ccc(Cl)cc3)n2)n1
Temperature: 88 °C
Reaction time: 6 h
Yield: 99.7 %

Procedure:
4,6-Dichloro-2-(3,5-dimethyl-pyrazol-1-yl)-pyrimidine (3.5 g, 14.4 mmol) and 4-chloroaniline (3.7 g, 28.8 mmol) were suspended in water (120 mL) and ethanol (17 mL). Concentrated hydrochloric acid (0.6 mL, 7.2 mmol) was added and the mixture was heated to 88° C. over-night. Additional 4-chloroaniline (918 mg) was added and stirring was continued for six hours. The mixture was cooled to room temperature and diluted with water. The resulting solid was collected by filtration to give [6-chloro-2-(3,5-dimethylpyrazol-1-yl)-pyrimidin-4-yl]-(4-chloro-phenyl)-amine (4.8 g, 99%) as a white solid.
Reaction SMILES: [ClH:1].[Cl:2][CH2:3][CH2:4][CH2:5]/[C:6](=[CH:18]\[C:19]1[CH:24]=[CH:23][C:22]([N:25]2[CH:29]=[C:28]([CH3:30])[N:27]=[CH:26]2)=[C:21]([O:31][CH3:32])[CH:20]=1)/[C:7]([NH:9][NH:10]C(OC(C)(C)C)=O)=[O:8]>C(OCC)(=O)C>[ClH:2].[ClH:1].[Cl:2][CH2:3][CH2:4][CH2:5]/[C:6](=[CH:18]\[C:19]1[CH:24]=[CH:23][C:22]([N:25]2[CH:29]=[C:28]([CH3:30])[N:27]=[CH:26]2)=[C:21]([O:31][CH3:32])[CH:20]=1)/[C:7]([NH:9][NH2:10])=[O:8]
Reactant: COc1cc(/C=C(\CCCCl)C(=O)NNC(=O)OC(C)(C)C)ccc1-n1cnc(C)c1
Agent: Cl
Solvent: CCOC(C)=O
Product: COc1cc(/C=C(\CCCCl)C(=O)NN)ccc1-n1cnc(C)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 4 N hydrochloric acid in ethyl acetate (1 mL) was added to a solution of tert-butyl N′-{5-chloro-2-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-(E)-methylidene}pentanoyl}hydrazinecarboxylate (222 mg) in ethyl acetate (1 mL), and the reaction solution was stirred at room temperature for two hours. The reaction solution was concentrated under reduced pressure to obtain 208 mg of the title compound. The property values of the compound are as follows.