Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:21]=[CH:20][C:19]([NH:22][CH2:23][CH2:24]Cl)=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2)=[O:5].[CH3:26][N:27]1[C:31]([CH2:32][CH2:33][NH2:34])=[CH:30][N:29]=[CH:28]1.C(N(CC)C(C)C)(C)C.[I-].[K+].[Na].C(=O)([O-])O>C(O)CCC>[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([NH:22][CH2:23][CH2:24][NH:34][CH2:33][CH2:32][C:31]2[N:27]([CH3:26])[CH:28]=[N:29][CH:30]=2)=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2)=[O:5]
Reactant: O=C(NCC12CC3CC(CC(C3)C1)C2)c1cc(NCCCl)ccc1Cl
Reactant: Cn1cncc1CCN
Agent: O=C([O-])O
Agent: [I-]
Agent: [K+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CCCCO
Product: Cn1cncc1CCNCCNc1ccc(Cl)c(C(=O)NCC23CC4CC(CC(C4)C2)C3)c1
Yield: 43 %

Procedure:
2-Chloro-5-[(2-chloroethyl)amino]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (Example 29c, 0.100 g), 3-methylhistamine (0.200 g), N,N-diisopropylethylamine (0.5 ml), potassium iodide (0.040 g) and n-butanol (4 ml) were heated together in a sealed tube at 110° C. for 24 h. The solution was cooled, poured into saturated aqueous sodium to hydrogencarbonate solution and extracted into ethyl acetate. The extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified on silica gel (eluant 19:1:0.1 dichloromethane/methanol/ammonia) to afford the title compound as a gum (0.053 g).
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][C:5]1[CH:10]=[C:9](Cl)[CH:8]=[C:7]([NH:12][CH2:13][CH2:14][OH:15])[C:6]=1[N+:16]([O-:18])=[O:17].[CH2:19]([CH2:21][NH2:22])[OH:20].Cl>>[OH:1][CH2:2][CH2:3][NH:4][C:5]1[CH:10]=[C:9]([NH:22][CH2:21][CH2:19][OH:20])[CH:8]=[C:7]([NH:12][CH2:13][CH2:14][OH:15])[C:6]=1[N+:16]([O-:18])=[O:17]
Reactant: NCCO
Reactant: O=[N+]([O-])c1c(NCCO)cc(Cl)cc1NCCO
Agent: Cl
Product: O=[N+]([O-])c1c(NCCO)cc(NCCO)cc1NCCO
Temperature: 0 °C

Procedure:
0.0072 mole (2 g) of 2-(β-hydroxyethyl)amino-6-(β-hydroxyethyl)amino-4-chloronitrobenzene, synthesized in stage 1 of example 2, was heated at 100°-110° C. with 6 ml of ethanolamine for 6 hours. The reaction medium was diluted with ice water then brought to neutrallity by addition of concentrated hydrochloric acid to precipitate out the desired product. After filtering and hot drying under vacuum in the presence of P2O5, it was recrystallized from 96° ethanol. It melted at 200° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]3[CH:15]=[N:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=3)=[N:12][C:11]([OH:22])=[N:10]2)=[CH:5][CH:4]=1.C(=O)([O-])[O-].[K+].[K+].I[CH2:30][C:31]([F:34])([F:33])[F:32].C(OCC)(=O)C>CS(C)=O>[CH3:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([C:13]2[N:9]([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[N:10]=[C:11]([O:22][CH2:30][C:31]([F:34])([F:33])[F:32])[N:12]=2)=[CH:15][N:16]=1
Reactant: FC(F)(F)CI
Reactant: COc1ccc(-n2nc(O)nc2-c2ccc(OC)nc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: COc1ccc(-n2nc(OCC(F)(F)F)nc2-c2ccc(OC)nc2)cc1
Temperature: 100 °C
Yield: 23.5 %

Procedure:
A mixture of 1-(4-methoxyphenyl)-5-(6-methoxypridin-3-yl)-1H-1,2,4-triazol-3-ol (200 mg, 0.67 mmol), potassium carbonate (278 mg, 2.01 mmol), and 2-iodo-1,1,1-trifluoroethane (0.198 mL, 2.01 mmol) in dimethylsulfoxide (1 mL) were heated at 100° C. for 1 hour. After cooling, ice water and ethyl acetate were poured into the mixture and the organic layer was separated, washed with brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure. The residue was purified by column chromatography (toluene-ethyl acetate 10:1). The desired product was washed with hexane to give 2-methoxy-5-(1-(4-methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1H-1,2,4-triazole-5-yl)pyridine. (60 mg, 23.5% yield)
Reaction SMILES: [C:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[O:12][CH3:13])(=[O:3])[CH3:2].[I:14]Cl>C(Cl)Cl>[C:1]([O:4][C:5]1[CH:10]=[C:9]([I:14])[C:8]([F:11])=[CH:7][C:6]=1[O:12][CH3:13])(=[O:3])[CH3:2]
Reactant: ClI
Reactant: COc1cc(F)ccc1OC(C)=O
Solvent: ClCCl
Product: COc1cc(F)c(I)cc1OC(C)=O
Temperature: 50 °C
Reaction time: 4 h
Yield: 85.5 %

Procedure:
To a solution of 64A (850 mg, 4.6 mmol) in CH2Cl2 (5.0 mL) was added ICl (1.0 M in CH2Cl2, 10.2 mL, 10.2 mmol). The mixture was stirred at 50° C. for 4 h and then at rt for 18 h. The reaction was quenched by a sat. solution of NaHCO3. After extraction with CH2Cl2, the organic layer was washed with a solution of Na2S2O3, brine and dried over Na2SO4. After evaporation of the solvent, the crude product was purified by column chromatography (EtOAc:hexanes=1:4) to give 64B (1.22 g, 80% yield) as a solid. 1H NMR (400 MHz, CDCl3) δ ppm 2.29 (s, 3H) 3.81 (s, 3H) 6.73 (d, J=9.23 Hz, 1H) 7.35 (d, J=6.59 Hz, 1H).
Reaction SMILES: C([BH3-])#N.[Na+].[OH:5][CH2:6][CH2:7][C:8]1[NH:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2.O>C(O)(=O)C>[OH:5][CH2:6][CH2:7][CH:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:9]1
Reactant: OCCc1cc2ccccc2[nH]1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: OCCC1Cc2ccccc2N1
Reaction time: 24 h
Yield: 98.8 %

Procedure:
Sodium cyanoborohydride (63 g) is added in portions to a stirred solution of 2-(2-hydroxyethyl)indole (43 g) in acetic acid (750 cc), whilst cooling the reaction mixture with a bath of cold water so as not to exceed 20° C. The mixture is stirred for 24 hours at this temperature. It is then concentrated to about 100 cc at 50° C. under reduced pressure (20 mm Hg). The residue is taken up in a mixture of water and ice (500 cc), the resulting mixture is rendered alkaline to pH 10 with an aqueous solution of sodium hydroxide and extraction is carried out with diethyl ether (3×300 cc). The organic extracts are combined, washed with water (50 cc), dried over magnesium sulphate and filtered and the filtrate is evaporated to dryness at 40° C. under reduced pressure (20 mm Hg). 2-(2-Hydroxyethyl)indoline (43 g) is obtained in the form of a yellow oil (mass spectrum m/e=163).
Reaction SMILES: [OH-].[K+].[CH:3]1[C:12]2[CH2:11][CH2:10][CH2:9][CH2:8][C:7]=2[CH:6]=[CH:5][C:4]=1[OH:13].[CH3:14][C:15]1[CH:16]=[C:17]([CH:22]=[CH:23][CH:24]=1)[O:18][CH2:19][CH2:20]Cl>O>[CH3:14][C:15]1[CH:16]=[C:17]([CH:22]=[CH:23][CH:24]=1)[O:18][CH2:19][CH2:20][O:13][C:4]1[CH:5]=[CH:6][C:7]2[CH2:8][CH2:9][CH2:10][CH2:11][C:12]=2[CH:3]=1
Reactant: Oc1ccc2c(c1)CCCC2
Reactant: Cc1cccc(OCCCl)c1
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: Cc1cccc(OCCOc2ccc3c(c2)CCCC3)c1

Procedure:
4.0 g (0.06 mol) of 85% potassium hydroxide was dissolved in 25 g of distilled water and 7.4 g (0.05 mol) of 5,6,7,8-tetrahydro-β-naphthol was dissolved in the formed solution. 8.5 g (0.05 mol) of 2-(3-methylphenoxy)ethyl chloride was added to the solution and the mixture was stirred under reflux for 3 h.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:18])[C:7]=1[CH2:8][S:9][C:10]1[N:15]=[C:14](O)[CH:13]=[C:12]([CH3:17])[N:11]=1.P(Cl)(Cl)([Cl:21])=O>>[Cl:21][C:14]1[CH:13]=[C:12]([CH3:17])[N:11]=[C:10]([S:9][CH2:8][C:7]2[C:2]([Cl:1])=[CH:3][N:4]=[CH:5][C:6]=2[Cl:18])[N:15]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1cc(O)nc(SCc2c(Cl)cncc2Cl)n1
Product: Cc1cc(Cl)nc(SCc2c(Cl)cncc2Cl)n1
Temperature: 75 °C
Yield: 47.1 %

Procedure:
A mixture of 2-{[(3,5-dichloropyridin-4-yl)methyl]sulfanyl}-6-methylpyrimidin-4-ol (2.0 g, 6.62 mmol) and phosphoryl trichloride (20 mL) was heated at 75° C. for 1 hour. The solvent was evaporated, and the crude residue was extracted into ethyl acetate (2×100 mL). The organic layer was washed with 10% sodium bicarbonate solution and brine. The organic layer was separated, dried over anhydrous sodium sulfate, and filtered. The solvent was evaporated, and the residue was purified by CombiFlash using 0-5% methanol in dichloromethane to provide 4-chloro-2-{[(3,5-dichloropyridin-4-yl)methyl]sulfanyl}-6-methylpyrimidine as a white solid (1.01 g, 47.1% yield); 1H NMR (400 MHz, DMSO-d6): δ 2.45 (s, 3H), 4.70 s, 2H), 7.40 (s, 1H), 8.66 (d, 211); M+1 321.2.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[C:10]([C:14]3[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=3)([CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[Na+].[CH2:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[C:10]([C:14]3[CH:19]=[CH:18][C:17]([NH:34][CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:16][CH:15]=3)([CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CC2CC2(c2ccc(Br)cc2)C1
Reactant: NCc1ccccc1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CC2CC2(c2ccc(NCc3ccccc3)cc2)C1
Yield: 79.1 %

Procedure:
To a solution of 1-(4-bromo-phenyl)-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (Intermediate I, 3.5 g, 10.4 mmol) in toluene (20 mL) were added Pd2(dba)3 (47 mg, 0.05 mmol), BINAP (97 mg, 0.16 mmol), sodium tert-butoxide (2.0 g, 20.7 mmol) and benzyl amine (1.2 mL, 11.4 mmol). The resulting solution was refluxed for 4 h. After the completion of the reaction, the reaction mixture was adsorbed on silica gel and purified by column chromatography (silica gel, 4:6 EtOAc:Pet. ether) to yield the title compound (3.0 g, 80%) as yellow solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:19]2[CH2:23][C@H:22]([CH2:24]OS(C)(=O)=O)[O:21][C:20]2=[O:30])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][O:16][CH3:17])[C:10](=[O:18])[CH2:9]1.[N-:31]=[N+:32]=[N-:33].[Na+]>CN(C=O)C>[N:31]([CH2:24][C@@H:22]1[O:21][C:20](=[O:30])[N:19]([C:4]2[CH:5]=[CH:6][C:7]([N:8]3[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][O:16][CH3:17])[C:10](=[O:18])[CH2:9]3)=[C:2]([F:1])[CH:3]=2)[CH2:23]1)=[N+:32]=[N-:33]
Reactant: [N-]=[N+]=[N-]
Reactant: COCCN1CCN(c2ccc(N3C[C@H](COS(C)(=O)=O)OC3=O)cc2F)CC1=O
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCCN1CCN(c2ccc(N3C[C@H](CN=[N+]=[N-])OC3=O)cc2F)CC1=O
Temperature: 80 °C
Yield: 88.3 %

Procedure:
(5R)-3-(3-Fluoro-4-{4-(2-methoxyethyl)-3-oxopiperazin-1-yl}phenyl)-5-(methanesulfonyl-oxymethyl)oxazolidin-2-one (990 mg) was dissolved in dry DMF (30 ml), sodium azide (868 mg) was added, and the mixture heated at 80° C. for 4 hours. The mixture was evaporated to dryness, and the residue dissolved in ethyl acetate and washed with three portions of water. The aqueous layer was back-extracted with two portions of ethyl acetate, and the combined organic extracts dried over MgSO4. Evaporation gave (5R)-5-azidomethyl-3-(3-fluoro-4-{4-(2-methoxyethyl)-3-oxopiperazin-1-yl}phenyl)oxazolidin-2-one (770 mg) which was used without further purification.
Reaction SMILES: C([C@@H]1CO[C:10](=O)[N:9]1[C:14](=[O:36])[C@H:15]([CH2:19][C:20]1[C:25]([Cl:26])=[CH:24][C:23]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:22][C:21]=1[Cl:35])[CH2:16]C=O)C1C=CC=CC=1.N[C@H:38]1[CH2:43][CH2:42][C@H:41]([OH:44])[CH2:40][CH2:39]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(O)(=O)C>ClCCCl>[CH2:28]([O:27][C:23]1[CH:22]=[C:21]([Cl:35])[C:20]([CH2:19][C@@H:15]2[CH2:16][CH2:10][N:9]([C@H:38]3[CH2:43][CH2:42][C@H:41]([OH:44])[CH2:40][CH2:39]3)[C:14]2=[O:36])=[C:25]([Cl:26])[CH:24]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: O=CC[C@@H](Cc1c(Cl)cc(OCc2ccccc2)cc1Cl)C(=O)N1C(=O)OC[C@H]1Cc1ccccc1
Reactant: N[C@H]1CC[C@H](O)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Solvent: CC(=O)O
Product: O=C1[C@H](Cc2c(Cl)cc(OCc3ccccc3)cc2Cl)CCN1[C@H]1CC[C@H](O)CC1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
Mix (R)-4-((R)-4-benzyl-2-oxo-oxazolidin-3-yl)-3-(4-benzyloxy-2,6-dichloro-benzyl)-4-oxo-butyraldehyde (Preparation 10) (3.054 g, 5.8 mmol), trans-4-amino-cyclohexanol (1.35, 11.6 mmol), NaBH(OAc)3 (5.18 g, 23.21 mmol) and acetic acid (0.63 mL, 11.2 mmol) in 50 mL of 1,2-dichloroethane. Stir for 12 hours at room temperature. Quench with saturated solution of NaHCO3 and extract with ethyl acetate. Wash the extract with brine. Dry over magnesium sulfate, filter, and concentrate. After flash column chromatography receive 1.39 g (54%) of the title compound: Mass spectrum (apci) m/z=448 (M+H).
Reaction SMILES: C[Si](Cl)(C)C.[CH3:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([N+:31]([O-:33])=[O:32])=[C:12]([CH2:14][C:15]([NH:17][CH:18]2[CH2:23][CH2:22][N:21]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:20][CH2:19]2)=O)[CH:13]=1.[BH4-].[Li+].Cl>O1CCCC1.O>[CH3:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([N+:31]([O-:33])=[O:32])=[C:12]([CH2:14][CH2:15][NH:17][CH:18]2[CH2:19][CH2:20][N:21]([CH2:24][C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH2:22][CH2:23]2)[CH:13]=1
Reactant: COc1ccc([N+](=O)[O-])c(CC(=O)NC2CCN(Cc3ccccc3)CC2)c1
Agent: C[Si](C)(C)Cl
Agent: Cl
Agent: [BH4-]
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc([N+](=O)[O-])c(CCNC2CCN(Cc3ccccc3)CC2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
34.0 ml (268.2 mmol) of trimethylsilyl chloride were slowly added dropwise to a solution of 27.0 g (70.4 mmol) of 5-methoxy-2-nitro-N-[1-(phenylmethyl)-4-piperidinyl]-benzeneacetamide in 400 ml of anhydrous tetrahydrofuran and then stirred for another 1 hour at ambient temperature. 4.9 g (213.7 mmol) of lithium borohydride were added batchwise, stirring was continued for another 30 minutes at ambient temperature and then for 4 hours at reflux temperature. After cooling, 25 ml of water and 25 ml of semiconcentrated hydrochloric acid were added dropwise one after the other and the mixture was refluxed for 90 minutes. It was left to stand overnight at ambient temperature, then cooled in an ice bath and the precipitate formed was suction filtered. The aqueous phase of the filtrate was made ammoniacal and extracted exhaustively with EE. The combined ethyl acetate extracts were dried with sodium sulphate, then combined with ethereal hydrogen chloride solution until the precipitation ended. The product precipitated was combined with the earlier precipitate, presumed to be the dihydrochloride of the desired compound, suspended in ethanol and suction filtered. The filter cake was dissolved in 100 ml of water, the solution was made ammoniacal and extracted exhaustively with EE. Conventional, working up of the ethyl acetate extracts yielded a pale yellow oil, Rf 0.69 (El D). Yield: 11.3 g (43% of theoretical).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]([CH3:13])[CH2:11]O)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:14]1(=[O:24])[NH:18][C:17](=[O:19])[C:16]2=[CH:20][CH:21]=[CH:22][CH:23]=[C:15]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]([CH3:13])[CH2:11][N:18]2[C:14](=[O:24])[C:15]3[C:16](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:17]2=[O:19])=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: C[C@@H](CO)c1ccc([N+](=O)[O-])cc1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: C[C@@H](CN1C(=O)c2ccccc2C1=O)c1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 97.2 %

Procedure:
A 250 mL three necked round bottom flask equipped with a mechanical stirrer, addition funnel, thermometer, and a reflux condenser is charged with (2R)-2-(4-nitrophenyl)propan-1-ol (2.0 g, 11.04 mmol), phthalimide (1.62 g, 11.04 mm), triphenylphosphine (4.3 g, 16.59 mmol) and THF (50.0 mL) at room temperature. To this solution was added DEAD (2.6 mL, 16.59 mmol) over a period of 5 minutes (reaction exothermed to reflux by the end of addition). The reaction was then stirred to room temperature overnight for convenience, quenched with water (50.0 mL) and extracted organic with methylene chloride (50.0 mL). The organic layer was then dried with anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure at 50° C. to an oil (11.62 g). Plug filtration of the oil over silica gel with 1:1 ethyl acetate/hexane (470.0 mL) and subsequent concentration of the fractions containing product afforded a light yellow precipitate. The precipitate was then dried in a house vacuum at 40° C. to provide 2-[(2R)-2-(4-nitrophenyl)propyl]isoindoline-1,3-dione (3.32 g, 96.9%); 1H nmr (CDCl3, 300 MHz) δ 1.50 (d, 3H, J=6.74 Hz), 3.45 (m, 1H), 3.89-3.95 (m, 2H), 7.5 (d, 2H), 7.67 (m, 2H), 7.68 (m, 2H), 8.10 (d, 2H); 13C nmr (CDCl3, 300 MHz δ 19.21, 38.90, 44.45, 123.59, 123.99, 128.50, 131.86, 134.35, 151.13, 168.34.
Reaction SMILES: [CH3:1][C@@H:2]([C@@H:10]1[C@@:14]2([CH3:29])[CH2:15][CH2:16][C@@H:17]3[C@@:22]4([CH3:28])[CH2:23][CH2:24][C@H:25]([OH:27])[CH2:26][C:21]4=[CH:20][CH:19]=[C:18]3[C@@H:13]2[CH2:12][CH2:11]1)/[CH:3]=[CH:4]/[C@@H:5]([CH:7]([CH3:9])[CH3:8])[CH3:6].[C:30](OC(=O)C)(=[O:32])[CH3:31].O>N1C=CC=CC=1>[C:30]([O:27][C@H:25]1[CH2:24][CH2:23][C@@:22]2([CH3:28])[C:21](=[CH:20][CH:19]=[C:18]3[C@@H:17]2[CH2:16][CH2:15][C@@:14]2([CH3:29])[C@H:13]3[CH2:12][CH2:11][C@@H:10]2[C@H:2]([CH3:1])/[CH:3]=[CH:4]/[C@H:5]([CH3:6])[CH:7]([CH3:8])[CH3:9])[CH2:26]1)(=[O:32])[CH3:31]
Reactant: CC(C)[C@@H](C)/C=C/[C@@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Reactant: CC(=O)OC(C)=O
Solvent: O
Solvent: c1ccncc1
Product: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC=C3[C@@H]4CC[C@H]([C@H](C)/C=C/[C@H](C)C(C)C)[C@@]4(C)CC[C@@H]32)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 73.6 %

Procedure:
To a solution of 50 gm (0.13 mol) of ergosterol (1) in 300 ml of anhydrous pyridine was added 33.3 ml (0.35 mol) of acetic anhydride. The mixture was stirred at room temperature overnight and then 600 ml of water was added. The precipitate was filtered and washed three times with 200 ml portions of acetonitrile and then air dried to yield 42.0 g (74%) of (2).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C@@H:18]3[CH2:22][O:21]C(C)(C)[O:19]3)=[CH:12][CH:11]=2)[C:5]([C:25]#[N:26])=[C:4]([S:27][CH2:28][C:29]2[N:30]=[C:31]([C:34]3[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=3)[O:32][CH:33]=2)[N:3]=1.O>C(O)(=O)C>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:11]=[CH:12][C:13]([O:16][CH2:17][C@@H:18]([OH:19])[CH2:22][OH:21])=[CH:14][CH:15]=2)[C:5]([C:25]#[N:26])=[C:4]([S:27][CH2:28][C:29]2[N:30]=[C:31]([C:34]3[CH:35]=[CH:36][C:37]([Cl:40])=[CH:38][CH:39]=3)[O:32][CH:33]=2)[N:3]=1
Reactant: CC1(C)OC[C@@H](COc2ccc(-c3c(C#N)c(N)nc(SCc4coc(-c5ccc(Cl)cc5)n4)c3C#N)cc2)O1
Solvent: O
Solvent: CC(=O)O
Product: N#Cc1c(N)nc(SCc2coc(-c3ccc(Cl)cc3)n2)c(C#N)c1-c1ccc(OC[C@@H](O)CO)cc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
400 mg (0.70 mmol) of the compound from Example 39A were initially charged in 17 ml of acetic acid, and 8.6 ml of water were then added carefully. The mixture was stirred at RT for 12 h. The reaction mixture was concentrated on a rotary evaporator, and the residue was then purified directly by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5). Removal of the solvent on a rotary evaporator gave the product as a solid.
Reaction SMILES: [F:1][C@:2]12[C@@H:22]([OH:23])[CH2:21][C@@:20]3([CH3:24])[C@@H:12]([CH2:13][CH:14]=[C:15]3[C:16](=[O:19])[CH2:17]O)[C@@H:11]1[CH2:10][CH2:9][C:8]1[C@:3]2([CH3:26])[CH:4]=[CH:5][C:6](=[O:25])[CH:7]=1.[I-:27].[Na+]>CC(C)=O>[F:1][C@:2]12[C@@H:22]([OH:23])[CH2:21][C@@:20]3([CH3:24])[C@@H:12]([CH2:13][CH:14]=[C:15]3[C:16](=[O:19])[CH2:17][I:27])[C@@H:11]1[CH2:10][CH2:9][C:8]1[C@:3]2([CH3:26])[CH:4]=[CH:5][C:6](=[O:25])[CH:7]=1
Reactant: C[C@]12C=CC(=O)C=C1CC[C@H]1[C@@H]3CC=C(C(=O)CO)[C@@]3(C)C[C@H](O)[C@@]12F
Reactant: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: C[C@]12C=CC(=O)C=C1CC[C@H]1[C@@H]3CC=C(C(=O)CI)[C@@]3(C)C[C@H](O)[C@@]12F
Yield: 76.6 %

Procedure:
A solution of 2.0 g of 9-fluoro-11β,21-dihydroxypregna-1,4,16-triene-3,20-dione, 21-methanesulfonate in 100 ml of acetone is refluxed with 3 g of sodium iodide under nitrogen for about 17 hours. The solid is filtered off and washed with 50 ml of acetone. The filtrate is evaporated in vacuo. The residue is redissolved in chloroform-methanol (9:1), washed with water, dried over anhydrous sodium sulfate and evaporated in vacuo to give 2.0 g of the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]([CH:11]=[O:12])=[CH:9][CH:10]=1)=[O:5])[CH3:2].[C-]#N.[K+].[CH3:16][C:17](O)=[O:18]>CCO.O=[Mn]=O>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]([C:11]([O:18][CH2:17][CH3:16])=[O:12])=[CH:9][CH:10]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1ccc(C=O)[nH]1
Reactant: CC(=O)O
Agent: O=[Mn]=O
Agent: [C-]#N
Agent: [K+]
Solvent: CCO
Product: CCOC(=O)c1ccc(C(=O)OCC)[nH]1
Reaction time: 8 h
Yield: 76.7 %

Procedure:
To a mixture of 406A (167 mg, 1.0 mmol), KCN (325.6 mg, 5.0 mmol) in anhydrous EtOH (20 ml) was added AcOH (85.9 μl, 1.5 mmol) followed by activated MnO2 (1.643 g, 20 mmol). The reaction was stirred overnight. After workup, the residue was purified by silica gel flash column chromatography to give 406B (162 mg, 77%) as a pinkish solid (25% EtOAc—hexanes).
Reaction SMILES: [C:1]([CH2:9][C:10]([O:12][CH3:13])=[O:11])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>CO>[C:2]1([CH:1]([OH:8])[CH2:9][C:10]([O:12][CH3:13])=[O:11])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)CC(=O)c1ccccc1
Solvent: CO
Product: COC(=O)CC(O)c1ccccc1
Temperature: 50 °C
Reaction time: 14 h

Procedure:
A2.3 mg (0.0014 mmol) portion of the thus obtained complex, 0.5 g (2.8 mmol) of methyl benzoylacetate and 2 ml of methanol were put into a stainless steel autoclave and stirred at 50° C. for 14 hours under a hydrogen pressure of 30 atm to obtain optically active methyl 3-phenyl-3-hydroxypropionate. When measured by HPLC, the conversion ratio was 100% and its optical purity was 96.5% ee.
Reaction SMILES: [OH-].[Na+:2].[N+:3]([C:6]1[CH:23]=[CH:22][C:9]([CH2:10][O:11][C:12]([NH:14][CH:15]([O:20][CH3:21])[C:16]([O:18]C)=[O:17])=[O:13])=[CH:8][CH:7]=1)([O-:5])=[O:4]>CO>[N+:3]([C:6]1[CH:7]=[CH:8][C:9]([CH2:10][O:11][C:12]([NH:14][CH:15]([O:20][CH3:21])[C:16]([O-:18])=[O:17])=[O:13])=[CH:22][CH:23]=1)([O-:5])=[O:4].[Na+:2]
Reactant: COC(=O)C(NC(=O)OCc1ccc([N+](=O)[O-])cc1)OC
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: COC(NC(=O)OCc1ccc([N+](=O)[O-])cc1)C(=O)[O-]

Procedure:
Aqueous sodium hydroxide (10 ml of a 2.5 N solution) is added dropwise over 15 minutes to a stirring solution of methyl N-(p-nitrobenzyloxycarbonyl)-α-methoxyglycinate (7.46 g, 25 mMol) in methanol (5 ml). The methanol is removed under reduced pressure and the aqueous residue is lyophilized to give sodium N-(p-nitrobenzyloxycarbonyl)-α-methoxyglycinate.
Reaction SMILES: [F:1][CH:2]([C:10](=[O:40])[CH2:11][C@H:12]1[C@@H:16]([O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[CH2:15][C@@H:14]([O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[C@@H:13]1[CH2:31][CH2:32][CH:33]([OH:39])[CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH3:9])=[O:7].CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O>[F:1][CH:2]([C:10](=[O:40])[CH2:11][C@H:12]1[C@@H:16]([O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[CH2:15][C@@H:14]([O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[C@@H:13]1[CH2:31][CH2:32][C:33](=[O:39])[CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH3:9])=[O:7]
Reactant: CCCCCC(O)CC[C@@H]1[C@@H](CC(=O)C(F)CCCC(=O)OC)[C@@H](OC2CCCCO2)C[C@H]1OC1CCCCO1
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)=O
Product: CCCCCC(=O)CC[C@@H]1[C@@H](CC(=O)C(F)CCCC(=O)OC)[C@@H](OC2CCCCO2)C[C@H]1OC1CCCCO1

Procedure:
To a solution of methyl 5(RS)-fluoro-6-oxo-7-{(1R,2R,3R,5S)-2-[3(RS)-hydroxy-1-octyl]-3,5-bis-tetrahydropyranyloxy-cyclopentyl]-6-oxo-heptanoate (54) (0.30 g) in acetone was added Jones reagent (2.60 M, 0.6 ml) and the resultant mixture was stirred at -30° C. for 1.5 hours. The reaction mixture was treated in the conventional manner and the obtained crude product was subjected to silica gel column chromatography to give the title compound (55) as a mixture of diastereomers.