Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][C:3]1[CH:21]=[CH:20][C:6]([O:7][CH2:8][C:9]2[N:10]=[C:11]([C:15]3[O:16][CH:17]=[CH:18][CH:19]=3)[O:12][C:13]=2[CH3:14])=[C:5]([O:22][CH3:23])[CH:4]=1.[OH:24]/[N:25]=[C:26](/[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)\[CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30].[H-].[Na+].Cl>CN(C)C=O.O>[O:16]1[CH:17]=[CH:18][CH:19]=[C:15]1[C:11]1[O:12][C:13]([CH3:14])=[C:9]([CH2:8][O:7][C:6]2[CH:20]=[CH:21][C:3]([CH2:2][O:24]/[N:25]=[C:26](/[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)\[CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])=[CH:4][C:5]=2[O:22][CH3:23])[N:10]=1
Reactant: COC(=O)CC/C(=N\O)c1ccccc1
Reactant: COc1cc(CCl)ccc1OCc1nc(-c2ccco2)oc1C
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)CC/C(=N\OCc1ccc(OCc2nc(-c3ccco3)oc2C)c(OC)c1)c1ccccc1
Reaction time: 1 h
Yield: 64.1 %

Procedure:
To a stirred solution of 4-(4-chloromethyl-2-methoxyphenoxymethyl)-2-(2-furyl)-5-methyloxazole (1.65 g) and methyl E-4-hydroxyimino-4-phenylbutyrate (1.04 g) in N,N-dimethylformamide (20 ml) was added sodium hydride (60% in oil, 200 mg) at 0° C. After stirring for 1 hour, the reaction mixture was poured into water, neutralized with 1N hydrochloric acid, and extracted with ethyl acetate. The extract was washed with water, dried (MgSO4), and concentrated. The residue was purified by column chromatography on silica gel. Elution with ethyl acetate-hexane (1:4, v/v) gave methyl E-4-[4-[2-(2-furyl)-5-methyl-4-oxazolylmethoxy]-3-methoxybenzyloxyimino]-4-phenylbutyrate (1.60 g, yield 64%) as crystals. Recrystallization from ethyl acetate-hexane gave pale yellow prisms. m.p. 67-69° C.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=1)([O-])=[O:2].[Cl-].[NH4+]>[Zn].O>[C:7]1([CH3:10])[CH:8]=[CH:9][C:4]([NH:1][OH:2])=[CH:5][CH:6]=1
Reactant: Cc1ccc([N+](=O)[O-])cc1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: O
Product: Cc1ccc(NO)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 19.8 %

Procedure:
281 g (2.05 moles) of p-nitrotoluene, 125 g (2.35 moles) of ammonium chloride and 4 l of water were charged into a 10-l reaction flask. 310 g (4.74 moles) of zinc dust was added thereto at room temperature (i.e., about 20°-30° C.) over a period of 15 minutes while stirring the mixture, and the mixture was stirred for an additional 30 minutes. In this case, the temperature of the reaction system increased to 65° to 70° C. with stirring. Thereafter, the reaction mixture was filtered, and the filtrate was saturated with sodium chloride. The filtrate was allowed to stand in a cool place for 24 hours. The precipitated crystals were filtered, and recrystallized from 1 l of a benzene-petroleum ether (1:1 by volume) mixture to obtain 50 g of p-tolylhydroxyl amine.
Reaction SMILES: [NH2:1]C1C=CN=CC=1.C(N(CC)CC)C.[C:15](Cl)(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C(Cl)Cl>[C:15]([NH2:1])(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Nc1ccncc1
Reactant: O=C(Cl)c1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: NC(=O)c1ccccc1
Yield: 122.4 %

Procedure:
To a solution of 4-aminopyridine (3.00 g, 31.9 mmol) in CH2Cl2 (50 mL) at 0° C. was added triethylamine (6.70 mL, 47.9 mmol) and benzoyl chloride (3.70 mL, 31.9 mmol). The ice bath was removed and the resulting mixture was allowed to warm tort over 1.5 h. The reaction was quenched with saturated aqueous NaHCO3, extracted with CH2Cl2, washed with brine, dried (MgSO4) and concentrated. The crude product was recrystallized from EtOAc/hexanes to give 4.73 g (75% yield) of pure benzamide.
Reaction SMILES: Cl.[CH2:2]([O:4][C:5](=[O:17])[CH2:6][CH:7]([NH2:16])[C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1)[CH3:3].C(=O)([O-])[O-].[Na+].[Na+].C(N1[C:33](=[O:34])[C:32]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:31]2[C:30]1=[O:39])(OCC)=O>O.C(#N)C>[C:30]1(=[O:39])[N:16]([CH:7]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH3:15])=[CH:12][CH:13]=2)[CH2:6][C:5]([O:4][CH2:2][CH3:3])=[O:17])[C:33](=[O:34])[C:32]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:31]12
Reactant: CCOC(=O)N1C(=O)c2ccccc2C1=O
Reactant: CCOC(=O)CC(N)c1ccc(OC)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: CCOC(=O)CC(c1ccc(OC)cc1)N1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 75 %

Procedure:
To a stirred solution of 3-amino-3-(4-methoxyphenyl)propionic acid ethyl ester hydrochloride (1.00 g, 3.85 mmol) and sodium carbonate (0.41 g, 3.85 mmol) in 40 mL of water was added N-carboethoxyphthalimide (0.84 g, 3.85 mmol) in 10 mL of acetonitrile. The reaction was complete in one hour by TLC. The reaction mixture was partially concentrated to remove the acetonitrile. To the resulting mixture was added 0.5 mL of ethyl ether and the mixture was stirred for 1 hour at room temperature. The resulting slurry was filtered and the solid was washed with copious amounts of water. The solid was air-dried overnight to afford 1.02 g (75%) of ethyl 3-phthalimido-3-(4-methoxyphenyl)propionate as a white gum: mp 32° C.; 1H NMR (DMSO-d6, 250 MHz)δ 7.86 (m, 4H), 6.90-7.37 (M, 4H), 5.66 (dd, 1H J1=7.5, J2=2.5), 4.00 (d, 2H, J=7.5), 3.3-3.6 (M, 2H), 1.04 (t, 3H, J=7.5 Hz); 13C (DMSO-d6)δ 170.1, 167.5, 158.7, 134.7, 131.0, 130.5, 128.3, 123.2, 113.88, 60.1, 55.0, 49.5, 35.7, 13.8. Anal. Calcd for C20H19NO5 : C, 67.98; H, 5.42; N, 3.90; Found C, 67.78; H, 5.30; N, 3.92.
Reaction SMILES: [CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][C:8]([NH:12][C:13]([C:15]3[C:16]([C:21]4[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=4)=[CH:17][CH:18]=[CH:19][CH:20]=3)=[O:14])=[CH:9][CH:10]=2)[CH:5]=[C:4]1[C:31]([OH:33])=O)[CH3:2].Cl.[NH2:35][C@@H:36]([C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[C:37]([NH:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38].CCN(C(C)C)C(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[CH2:40]([NH:39][C:37](=[O:38])[C@@H:36]([NH:35][C:31]([C:4]1[N:3]([CH2:1][CH3:2])[C:11]2[C:6]([CH:5]=1)=[CH:7][C:8]([NH:12][C:13]([C:15]1[C:16]([C:21]3[CH:22]=[CH:23][C:24]([C:27]([F:30])([F:28])[F:29])=[CH:25][CH:26]=3)=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:14])=[CH:9][CH:10]=2)=[O:33])[C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1)[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1
Reactant: N[C@H](C(=O)NCc1ccccc1)c1ccccc1
Reactant: CCn1c(C(=O)O)cc2cc(NC(=O)c3ccccc3-c3ccc(C(F)(F)F)cc3)ccc21
Agent: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCn1c(C(=O)N[C@H](C(=O)NCc2ccccc2)c2ccccc2)cc2cc(NC(=O)c3ccccc3-c3ccc(C(F)(F)F)cc3)ccc21
Reaction time: 8 h
Yield: 71 %

Procedure:
1-Ethyl-5-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-1H-indole-2-carboxylic acid (0.05 g, 0.11 mmol) and (S)-2-Amino-N-benzyl-2-phenyl-acetamide hydrochloride (0.031 g, 0.11 mmol) were combined in DCM (3 mL) and DIEA (1.1 mL) was added to the above mixture. PyBroP (0.077 g, 0.17 mmol) was added to the above mixture in one portion. The mixture which was resulted was stirred overnight. The crude mixture was then purified by HPLC to furnish the desired product (52.7 mg). HPLC retention time 16.892 min.; Mol. Wt. (calc) 674.7; MS (found) 675.2.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:24])=[C:8]2[C:14]([Br:15])=[C:13]([Br:16])[N:12]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:9]2=[CH:10][N:11]=1)=[O:5])[CH3:2].C1C(=O)N([Br:32])C(=O)C1>CC#N>[CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:24])=[C:8]2[C:14]([Br:15])=[C:13]([Br:16])[N:12]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:9]2=[C:10]([Br:32])[N:11]=1)=[O:5])[CH3:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)c1ncc2c(c1O)c(Br)c(Br)n2-c1ccc(F)cc1
Solvent: CC#N
Product: CCOC(=O)c1nc(Br)c2c(c1O)c(Br)c(Br)n2-c1ccc(F)cc1

Procedure:
Prepared in analogy to that of Example 133(a) from 2,3-dibromo-1-(4-fluoro-phenyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester and NBS in MeCN. The title compound, ESI MS (m/z): 535 (M+H)+.
Reaction SMILES: [Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.[F:12][C:13]1[C:14]([CH2:26][OH:27])=[C:15]([NH:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22])[CH:16]=[CH:17][CH:18]=1>C(Cl)Cl>[F:12][C:13]1[C:14]([CH:26]=[O:27])=[C:15]([NH:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:22])[CH3:23])[CH:16]=[CH:17][CH:18]=1
Reactant: CC(C)(C)C(=O)Nc1cccc(F)c1CO
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CC(C)(C)C(=O)Nc1cccc(F)c1C=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Pyridinium chlorochromate (596 mg, 2.76 mmol) was added to a solution of N-(3-fluoro-2-(hydroxymethyl)phenyl) pivalamide (415 mg, 1.84 mmol) in CH2Cl2 (50 mL) at 0° C. 5 min later the mixture was allowed stirring at room temperature for 3 hrs. The reaction mixture was passed through a thin pad layer of silica gel with CH2Cl2 (2×50 mL), concentrated on rotary vacuum, and purified on a flash chromatography column eluting with 20˜50% EtOAc/hexanes (600 mL) to afford the expected product, N-(3-fluoro-2-formylphenyl)pivalamide, as a white solid (396 mg, 46% yield after five steps); 1H NMR (400 MHz, CDCl3) δ ppm 1.33 (s, 9H), 6.76-6.83 (m, 1H), 7.54 (td, J=8.44, 6.55 Hz, 1H), 8.56 (d, J=8.56 Hz, 1H), 10.38 (s, 1H), 11.57 (s, 1H); Mass spec. 224.11 (MH+), Calc. for C12H14FNO2 223.1.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[N:5]([CH3:9])[CH:6]=[CH:7][CH:8]=1.[C:10]1([S:16](Cl)(=[O:18])=[O:17])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>>[C:10]1([S:16]([NH:1][CH2:2][CH2:3][C:4]2[N:5]([CH3:9])[CH:6]=[CH:7][CH:8]=2)(=[O:18])=[O:17])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: Cn1cccc1CCN
Product: Cn1cccc1CCNS(=O)(=O)c1ccccc1

Procedure:
Prepared from 2-(2-aminoethyl)-1-methylpyrrole and benzenesulphonyl chloride analogously to Example A.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:14][OH:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[N+:16]([C:19]1[CH:26]=[CH:25][CH:24]=[C:23]([N+]([O-])=O)[C:20]=1[C:21]#[N:22])([O-:18])=[O:17].[H-].[Na+]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:14][O:15][C:23]1[CH:24]=[CH:25][CH:26]=[C:19]([N+:16]([O-:18])=[O:17])[C:20]=1[C:21]#[N:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: N#Cc1c([N+](=O)[O-])cccc1[N+](=O)[O-]
Reactant: CC(C)(C)OC(=O)N1CCCC[C@@H]1CO
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCCC[C@@H]1COc1cccc([N+](=O)[O-])c1C#N
Temperature: 25 °C
Reaction time: 18 h
Yield: 90.6 %

Procedure:
To a solution of (R)-tert-butyl-2-(hydroxymethyl)piperidine-1-carboxylate (Example 15f, 7.10 g, 33.0 mmol) and 2,6-dinitrobenzonitrile (6.37 g, 33.0 mmol) in THF (142 mL) cooled to −78° C., was added NaH (60% dispersion in oil, 1.45 g. 36.3 mmol). The reaction was allowed to warm to room temperature and stirring was continued for 18 hours. Upon completion, the reaction was cooled to 0° C. and quenched with water. The mixture was extracted with ethyl acetate, and the organic extracts were combined and dried over anhydrous Na2SO4, filtered, and concentrated. The residue was recrystallized from ethyl acetate/hexanes to afford (R)-tert-butyl-2-((2-cyano-3-nitrophenoxy)methyl)piperidine-1-carboxylate (10.8 g, 91%) as a yellow solid. MS 282 (MH+-boc).
Reaction SMILES: [NH2:1][C:2]1[C:10]([N+:11]([O-])=O)=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[H][H]>C1COCC1.CO.[Pd]>[NH2:1][C:2]1[C:10]([NH2:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5]
Reactant: [H][H]
Reactant: NC(=O)c1cccc([N+](=O)[O-])c1N
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: NC(=O)c1cccc(N)c1N

Procedure:
The mixture of 206 g (1.14 mol) of 6 and 20.6 g of 10% Pd on charcoal in 824 ml of THF and 824 ml of methanol was hydrogenated with a total of 6 equivalents of hydrogen (130 l) at 2048° C. over 24 h. The mixture was filtrated and the solvents were evaporated.
Reaction SMILES: [OH-].[K+].[CH3:3][N:4]([CH3:10])[CH2:5][CH:6]([OH:9])[CH2:7]O.CS([O:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]/[CH:24]=[CH:25]\[CH2:26]/[CH:27]=[CH:28]\[CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])(=O)=O>C1(C)C=CC=CC=1>[CH2:16]([O:15][CH:5]([N:4]([CH3:10])[CH3:3])[CH:6]([O:9][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]/[CH:24]=[CH:25]\[CH2:26]/[CH:27]=[CH:28]\[CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[CH3:7])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]/[CH:24]=[CH:25]\[CH2:26]/[CH:27]=[CH:28]\[CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]
Reactant: CN(C)CC(O)CO
Reactant: CCCCC/C=C\C/C=C\CCCCCCCCOS(C)(=O)=O
Agent: [K+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: CCCCC/C=C\C/C=C\CCCCCCCCOC(C)C(OCCCCCCCC/C=C\C/C=C\CCCCC)N(C)C
Reaction time: 14.5 h

Procedure:
In a nitrogen atmosphere, dehydrated toluene (30 ml) and potassium hydroxide (4.9 g, 87.0 mmol) were added to a four-necked flask, and 3-(dimethylamino)-1,2-propanediol (0.57 g, 4.78 mmol: DAP) was dropped under agitation. Thereafter, linoleyl methane sulfonate (5.0 g, 14.5 mmol) was added, and reaction was effected at room temperature for 14.5 hours. The reaction was terminated because isomers increased to 0.079%, although remaining linoleyl methane sulfonate was 51.1% and, therefore, 5.0% or less was not satisfied (degree of conversion: 28.9%, integrated value of isomer: 0.079).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:9]([CH:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][CH2:12][C:11]2([CH3:21])[CH3:20])[CH:8]=[N:7][CH:6]=1)=[O:4].[Br:22]N1C(C)(C)C(=O)N(Br)C1=O>C(Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[N:9]([CH:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([Br:22])=[CH:12][C:11]2([CH3:21])[CH3:20])[CH:8]=[N:7][CH:6]=1)=[O:4]
Reactant: COC(=O)c1cncn1C1c2ccccc2CCC1(C)C
Reactant: CC1(C)C(=O)N(Br)C(=O)N1Br
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1cncn1C1c2ccccc2C(Br)=CC1(C)C
Temperature: 25 °C
Yield: 51.9 %

Procedure:
A solution of 8.5 g of 1-(2,2-dimethyltetralin-1-yl)-5-imidazolecarboxylic acid methyl ester in 100 ml of carbon tetrachloride is treated with 8.6 g of 1,3-dibromo-5,5-dimethylhydantoin and heated to reflux for 1 hour, while the reaction vessel is exposed to a 100W-irradiation lamp. The mixture is cooled to room temperature and concentrated to dryness. Chromatography of the residue at a silica gel column with methylene chloride affords 5.6 g of 1-(2,2-dimethyl-4-bromo-1,2-dihydronaphthalin-1-yl)-5-imidazolecarboxylic acid methyl ester in form of colourless crystals; mp. 101°-103° C.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]([C:6]([CH:14]2[CH2:16][CH2:15]2)=[C:7]([F:13])[C:8](OCC)=[O:9])=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>CCOCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([CH:14]2[CH2:16][CH2:15]2)=[C:7]([F:13])[CH2:8][OH:9])=[CH:17][CH:18]=1
Reactant: CCOC(=O)C(F)=C(c1ccc(Cl)cc1)C1CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: OCC(F)=C(c1ccc(Cl)cc1)C1CC1
Temperature: -55 °C
Reaction time: 1.5 h
Yield: 97 %

Procedure:
A solution of ethyl p-chloro-β-cyclopropyl-α-fluorocinnamate, (E)- and (Z)- (32.25 g, 0.12 mol) in ether is added dropwise to a mixture of lithium aluminum hydride (5.46 g, 0.144 mol) in ether while maintaining the temperature at -55° C. After the addition is complete, the reaction mixture is warmed to and stirred at -20° C. for 90 minutes, quenched sequentially with ethyl acetate, methanol and 2N hydrochloric acid, and extracted with ether. The organic extracts are combined, washed sequentially with water, saturated sodium hydrogen carbonate solution and water, dried over anhydrous sodium sulfate, and concentrated in vacuo to give the title product as a colorless oil (26.4 g, 97%).
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[CH2:8][C:7](=[O:9])[O:6][C:4](=[O:5])[CH2:3]1.[CH3:11][C:12]([O-:15])([CH3:14])[CH3:13].[K+]>C1COCC1.CCOCC>[C:12]([O:15][C:7](=[O:9])[CH2:8][C:2]([CH3:10])([CH3:1])[CH2:3][C:4]([OH:6])=[O:5])([CH3:14])([CH3:13])[CH3:11]
Reactant: CC1(C)CC(=O)OC(=O)C1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC(C)(CC(=O)O)CC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 69 %

Procedure:
3,3-Dimethylglutaric anhydride (6.5 g, 45.7 mmol) was dissolved in THF (75 mL) and the t-BuOK, 1M in THF (52.5 mL, 52.5 mmol) was added and the mixture was stirred at room temperature for one hour. The reaction mixture was then diluted with ether, washed with 1N HCl, brine (3×), dried (MgSO4), and concentrated to give 6.8 g (69%) of the desired product as a colorless oil. 1H NMR (DMSO-d6) 12.0 (br s, 1H), 2.22 (s, 4H), 1.39 (s, 9H), 1.03 (s, 6H).
Reaction SMILES: [OH:1][C:2]1[C:3]([CH3:19])=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:10][C:9]=2[CH3:18])[CH:5]=[CH:6][CH:7]=1.[C:20]([O:28][CH2:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][C:37]=1[CH2:38][O:39][C:40](=[O:47])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH2:33]Br)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>>[C:21]1([C:20]([O:28][CH2:29][C:30]2[CH:31]=[C:32]([CH:35]=[CH:36][C:37]=2[CH2:38][O:39][C:40]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[O:47])[CH2:33][O:1][C:2]2[C:3]([CH3:19])=[C:4]([C:8]3[CH:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:10][C:9]=3[CH3:18])[CH:5]=[CH:6][CH:7]=2)=[O:27])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: COC(=O)c1ccc(-c2cccc(O)c2C)c(C)c1
Reactant: O=C(OCc1ccc(CBr)cc1COC(=O)c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COC(=O)c1ccc(-c2cccc(OCc3ccc(COC(=O)c4ccccc4)c(COC(=O)c4ccccc4)c3)c2C)c(C)c1

Procedure:
In a manner similar to that of Example 1(i), by reaction of 515 mg (2 mmol) of methyl 3′-hydroxy-2,2′-dimethylbiphenyl-4-carboxylate with 880 mg (2 mmol) of 3,4-bis(benzoyloxymethyl)benzyl bromide and 300 mg (2.2 mmol) of potassium carbonate, the desired product is obtained in the form of a colourless oil (m=1.22 g; Y=99%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9](Cl)[C:10]([F:13])([F:12])[F:11])=[CH:4][CH:3]=1.[N-:15]=[N+:16]=[N-:17].[Na+].Cl.C(N(CC)CC)C>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:9]([C:10]([F:13])([F:12])[F:11])=[N:17][N:16]=[N:15]2)=[CH:4][CH:3]=1
Reactant: FC(F)(F)C(Cl)=Nc1ccc(Cl)cc1
Reactant: [N-]=[N+]=[N-]
Agent: Cl
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: FC(F)(F)c1nnnn1-c1ccc(Cl)cc1
Temperature: 25 °C
Yield: 92.1 %

Procedure:
Three grams (12.4 mmol) of N-(4-chlorophenyl)-2,2,2-trifluoroacetimidoyl chloride obtained in Example 11, 1.46 g (22.3 mmol) of sodium azide, 0.85 g (6.20 mmol) of triethylamine hydrochloride, and 30 ml of toluene were introduced into a 100 ml flask and reacted at 80° C. for 24.5 hours. After the reaction, the reaction solution was cooled to room temperature and washed with water (20 ml×2). The organic phase was dried over anhydrous magnesium sulfate for 1 hour, filtered, and then subjected to solvent removal by evaporation. The crude product thus obtained was purified by column chromatography (silica gel, ethyl acetate:hexane=3:7), resulting in 2.84 g of 1-(4-chlorophenyl)-5-(trifluoromethyl)-1H-tetrazole as a pale yellow oil (yield: 92.2%).
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([CH:8]([OH:13])[CH2:9][CH2:10][CH2:11][CH3:12])[CH:5]=[CH:4][CH:3]=1.[C:14](OC=C)(=[O:16])[CH3:15]>C1CCCCC1>[C:14]([O:13][C@@H:8]([C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([Br:1])[N:7]=1)[CH2:9][CH2:10][CH2:11][CH3:12])(=[O:16])[CH3:15]
Reactant: CCCCC(O)c1cccc(Br)n1
Reactant: C=COC(C)=O
Solvent: C1CCCCC1
Product: CCCC[C@@H](OC(C)=O)c1cccc(Br)n1
Reaction time: 7.5 h
Yield: 62.8 %

Procedure:
To a gently shaking solution of 1-(6-bromo-2-pyridinyl)-1-pentanol (1.00 g, 4.10 mmol) in dry cyclohexane (100 mL) was added Lipase PS-C “Amano” (Pseudomonas cepacia) (9.97 g) followed by vinyl acetate (1.5 mL, 16.27 mmol). Shaking was continued for 7.5 h with continual monitoring by chiral HPLC. The mixture was then filtered and the filtrate reduced under vacuum to give an oil which was purified by SPE (silica, 20 g cartridge) eluting with cyclohexane:EtOAc (gradient 50:1 to 2:1) to afford (1R)-1-(6-bromo-2-pyridinyl)pentyl acetate as an oil (737 mg, 63%). LC/MS: m/z 286.1/288.1 [M+H]+, Rt 3.38 min. Analytical chiral HPLC (25 cm Chiralpak AD) eluting with 2% EtOH in heptane, f=1.0 mL/min, wavelength 215 nm, (S-) Rt 5.1 min and (R-) Rt 5.4 min (43% ee) and the title compound as an oil (349 mg).
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:13][NH:12][C:11]2=[O:21])=[CH:6][CH:5]=1.[CH3:22][O:23][C:24](=[O:33])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]Br>CN(C=O)C>[CH3:22][O:23][C:24](=[O:33])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][N:12]1[CH:13]=[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:10]([C:7]2[CH:6]=[CH:5][C:4]([F:3])=[CH:9][CH:8]=2)[C:11]1=[O:21]
Reactant: O=c1[nH]cc(-c2ccccc2)n1-c1ccc(F)cc1
Reactant: COC(=O)CCCCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)CCCCCCCn1cc(-c2ccccc2)n(-c2ccc(F)cc2)c1=O

Procedure:
The product is product as described in example 1 from 2.16 g of NaH (80% suspension in mineral oil), 18.3 g of 1-(4-Fluorophenyl)-5-phenyl-4-imidazolin-2-one, 150 cc. of DMF, 17.1 g of 8-bromocaprylic acid methyl ester and 2.16 g of NaJ.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[CH2:5][C:6]1[O:10][N:9]=[C:8]([C:11]([OH:13])=O)[CH:7]=1.[Cl:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[N:23]([CH3:27])[CH:22]=[C:21]2[CH2:28][CH2:29][NH2:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[Cl:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[N:23]([CH3:27])[CH:22]=[C:21]2[CH2:28][CH2:29][NH:30][C:11]([C:8]1[CH:7]=[C:6]([CH2:5][C:4]2[CH:14]=[CH:15][CH:16]=[C:2]([F:1])[CH:3]=2)[O:10][N:9]=1)=[O:13]
Reactant: Cn1cc(CCN)c2cc(Cl)ccc21
Reactant: O=C(O)c1cc(Cc2cccc(F)c2)on1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cn1cc(CCNC(=O)c2cc(Cc3cccc(F)c3)on2)c2cc(Cl)ccc21
Yield: 36.8 %

Procedure:
A solution of 5-(3-fluorobenzyl)isoxazole-3-carboxylic acid (0.057 g; 0.257 mmol), 2-(5-chloro-1-methyl-1H-indol-3-yl)ethanamine (0.060 g; 0.284 mmol), HATU (0.108 g; 0.284 mmol) and N,N-diisopropylethylamine (0.112 mL; 0.649 mmol) in DMF (3 mL), was stirred at room temperature overnight. The reaction mixture was partitioned between ethyl acetate and sodium hydrogen sulfate, the organic layer was washed with sodium carbonate, brine, dried and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane) to yield 0.039 g (36%) of the title compound as a yellow solid.
Reaction SMILES: Br[CH2:2][C:3]1[O:8][C:7](=[O:9])[CH:6]=[C:5]([OH:10])[CH:4]=1.Cl.[OH-:12].[Na+]>O>[OH:10][C:5]1[CH:4]=[C:3]([CH2:2][OH:12])[O:8][C:7](=[O:9])[CH:6]=1
Reactant: O=c1cc(O)cc(CBr)o1
Reactant: [OH-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: O=c1cc(O)cc(CO)o1
Temperature: 50 °C
Yield: 69 %

Procedure:
6-Bromomethyl-4-hydroxypyran-2-one (21.1 parts) was dissolved in a solution of sodium hydroxide (4.1 parts) in water (800 parts) at 20°-25° C. This solution was added over about 2 hours to a solution of sodium hydroxide (34.2 parts) in water (3200 parts) at 50° C.±3° C. The mixture was stirred for a further hour at 50° C. before acidifying with 35% hydrochloric acid and distilling off the bulk of the water at 50° C./20 mm. The mixture was cooled to 20° C. and insoluble material was filtered off. The filtrate was saturated with sodium chloride and then extracted with ethyl acetate (15×125 parts). The combined extracts were dried over magnesium sulphate and the solvent removed at 40° C./20 mm to give 4-hydroxy-6-hydroxymethylpyran-2-one (10.2 parts, 69%).