Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([CH:3]([C:6]1[N:10]2[C:11]3[C:16]([NH:17][C:18](=[O:19])[C:9]2=[CH:8][N:7]=1)=[CH:15][C:14]([C:20]([OH:22])=O)=[CH:13][CH:12]=3)[CH2:4][CH3:5])[CH3:2].C(N1C=CN=C1)([N:25]1C=CN=C1)=O.N.O>CN(C)C=O>[CH2:4]([CH:3]([C:6]1[N:10]2[C:11]3[C:16]([NH:17][C:18](=[O:19])[C:9]2=[CH:8][N:7]=1)=[CH:15][C:14]([C:20]([NH2:25])=[O:22])=[CH:13][CH:12]=3)[CH2:1][CH3:2])[CH3:5]
Reactant: CCC(CC)c1ncc2c(=O)[nH]c3cc(C(=O)O)ccc3n12
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: N
Solvent: CN(C)C=O
Solvent: O
Product: CCC(CC)c1ncc2c(=O)[nH]c3cc(C(N)=O)ccc3n12

Procedure:
1-(1-Ethylpropyl)-4-oxo-4,5-dihydroimidazo[1,5-a]quinoxaline-7-carboxylic acid as synthesized in above Example 13, 300 mg was dissolved in 10 mL of N,N-dimethylformamide, and to the solution 1,1′-carbonyldiimidazole 275 mg was added little by little in nitrogen atmosphere. After another hour's stirring, ammonia gas was injected into the reaction liquid for 30 minutes, followed by an hour's stirring. Water 30 mL was added and the formed precipitate was recovered by filtration. The crystals were washed with water and dried by heating under reduced pressure to provide 250 mg of the title compound.
Reaction SMILES: [CH:1]1[N:5]([C@@H:6]2[O:10][C@H:9]([CH2:11]O)[C@@H:8]([OH:13])[C@H:7]2[OH:14])[C:4]([NH2:15])=[C:3]([C:16]([NH2:18])=[O:17])[N:2]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)[Cl:39].C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C)C=O.CO>[NH2:15][C:4]1[N:5]([C@@H:6]2[O:10][C@H:9]([CH2:11][Cl:39])[C@@H:8]([OH:13])[C@H:7]2[OH:14])[CH:1]=[N:2][C:3]=1[C:16]([NH2:18])=[O:17]
Reactant: NC(=O)c1ncn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c1N
Reactant: ClC(Cl)(Cl)Cl
Agent: O=P(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CO
Product: NC(=O)c1ncn([C@@H]2O[C@H](CCl)[C@@H](O)[C@H]2O)c1N

Procedure:
AICA riboside (1.00 g), triphenylphosphine (3.05 g) and carbon tetrachloride (1.15 ml) were stirred in dimethyl formamide (38 ml) at room temperature for 3 hours. The solution was diluted with methanol (15 ml), then concentrated under reduced pressure. The resulting yellow tar was chromatographed on silica gel, eluting with 4:1 methylene chloride:methanol. The like fractions were combined and concentrated under reduced pressure to afford a purple foam. The presence of triphenylphosphine oxide, as determined by 1H NMR, necessitated a second chromotographic step as above. Yield was 0.43 g of a white foam.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[NH:10][CH:9]=[CH:8]2)=[O:2].C[Li].[CH2:14](OCC)C.C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)(=O)C>[NH:10]1[C:11]2[C:7](=[CH:6][CH:5]=[CH:4][C:3]=2[CH:1]([OH:2])[CH3:14])[CH:8]=[CH:9]1
Reactant: CCOCC
Reactant: O=Cc1cccc2cc[nH]c12
Agent: O=C([O-])O
Agent: [Li]C
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(O)c1cccc2cc[nH]c12
Yield: 94.5 %

Procedure:
Add 7-formylindole (1.0 g, 6.89 mmol) in anhydrous tetrahydrofuran (15 ml) dropwise to a solution of 1.4M methyllithium in diethyl ether (12.2 ml, 17.1 mmol) at −78° C. After 15 minutes add saturated aqueous sodium bicarbonate (15 ml). Dilute with 1:1 ethyl acetate: diethyl ether, wash with saturated aqueous sodium bicarbonate followed by saturated aqueous sodium chloride, dry over magnesium sulfate, and concentrate under reduced pressure to provide desired compound (1.05 g, 94%) as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](=[O:11])[CH3:10])=[CH:4][C:3]=1[S:12](Cl)(=[O:14])=[O:13].ClC1C=CC(CC(=O)C)=CC=1S(N)(=O)=O.N.[CH2:32]([CH2:34][NH2:35])[OH:33]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](=[O:11])[CH3:10])=[CH:4][C:3]=1[S:12]([NH:35][CH2:34][CH2:32][OH:33])(=[O:14])=[O:13]
Reactant: CC(=O)Cc1ccc(Cl)c(S(=O)(=O)Cl)c1
Reactant: NCCO
Agent: CC(=O)Cc1ccc(Cl)c(S(N)(=O)=O)c1
Agent: N
Product: CC(=O)Cc1ccc(Cl)c(S(=O)(=O)NCCO)c1

Procedure:
This material is prepared from 2-chloro-5-(2-oxopropyl)-benzenesulphonyl chloride (32a) following the same procedure described for the preparation of 2-chloro-5-(2-oxo-propyl)-benzenesulfonamide (33a), replacing ammonia in this procedure with ethanolamine.
Reaction SMILES: Cl.[NH2:2][C@H:3]([C:5]([O:7][CH3:8])=[O:6])[CH3:4].Br[CH:10]([CH3:14])[C:11]([OH:13])=[O:12].[OH-].[Na+]>O1CCOCC1.O>[C:5]([CH:3]([NH:2][C@H:10]([C:11]([OH:13])=[O:12])[CH3:14])[CH3:4])([O:7][CH3:8])=[O:6]
Reactant: CC(Br)C(=O)O
Reactant: COC(=O)[C@H](C)N
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: COC(=O)C(C)N[C@@H](C)C(=O)O
Reaction time: 0.5 h

Procedure:
Neutralize a solution of 1.4 g of methyl L-alaninate HCl and 3.1 g of α-bromopropionic acid in a dioxane-water mixture to pH 9 with sodium hydroxide. Warm to 70° and hold for 30 minutes, keeping the pH at 8 to 9 by addition of sodium hydroxide as necessary. Cool, apply to a column of Dowex 50 (H+) ion exchange resin, wash with water, and elute with 2% pyridine in water. Combine the product fractions and freeze dry. Purify this crude by chromatography on an ion-exchange column of Dowex 50 (Na+) in 0.5 M sodium citrate buffer pH 3.3. Collect the product fractions, concentrate to a small volume in vacuo, and repeat the Dowex 50 (H+) chromatography. Freeze dry the product fractions to obtain the pure N-(1-carbomethoxyethyl)-alanine.
Reaction SMILES: F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[C:28]([N:35]1[CH2:43][CH2:42][CH:38]([C:39]([OH:41])=O)[CH2:37][CH2:36]1)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].CCN(C(C)C)C(C)C.[CH3:53][O:54][C:55]1[CH:60]=[CH:59][C:58]([CH:61]2[CH2:66][CH2:65][CH2:64][CH2:63][CH2:62]2)=[CH:57][C:56]=1[C:67]1[N:68]=[C:69]([NH2:72])[S:70][CH:71]=1>C(#N)C>[CH:61]1([C:58]2[CH:59]=[CH:60][C:55]([O:54][CH3:53])=[C:56]([C:67]3[N:68]=[C:69]([NH:72][C:39]([CH:38]4[CH2:37][CH2:36][N:35]([C:28]([O:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:29])[CH2:43][CH2:42]4)=[O:41])[S:70][CH:71]=3)[CH:57]=2)[CH2:62][CH2:63][CH2:64][CH2:65][CH2:66]1
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)O)CC1
Reactant: COc1ccc(C2CCCCC2)cc1-c1csc(N)n1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(C2CCCCC2)cc1-c1csc(NC(=O)C2CCN(C(=O)OC(C)(C)C)CC2)n1
Temperature: 25 °C
Reaction time: 24 h
Yield: 69.1 %

Procedure:
1.68 g of BOP, 0.75 g of Boc-isonipecotic acid and then 1.41 mL of DIPEA are added, at a temperature of 0° C., to a solution of 1 g of 4-(2-methoxy-5-cyclohexylphenyl)-1,3-thiazol-2-amine, obtained in preparation I.3, in 6 mL of acetonitrile. The medium is stirred at room temperature for 24 hours and then filtered. The solid thus obtained is rinsed with acetonitrile and then dried. 1.13 g of a white solid are thus obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:31])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[N:12]([CH2:24][C:25](F)=[O:26])[CH:11]3[C:28]([CH3:30])=[CH2:29])[C:5]2=[CH:4][CH:3]=1.[CH3:32][S:33]([N:36]1[CH2:41][CH2:40][CH:39]([NH2:42])[CH2:38][CH2:37]1)(=[O:35])=[O:34].CN1CCOCC1>CN(C)C1C=CN=CC=1.O1CCCC1>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:31])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[N:12]([CH2:24][C:25]([NH:42][CH:39]4[CH2:40][CH2:41][N:36]([S:33]([CH3:32])(=[O:35])=[O:34])[CH2:37][CH2:38]4)=[O:26])[CH:11]3[C:28]([CH3:30])=[CH2:29])[C:5]2=[CH:4][CH:3]=1
Reactant: C=C(C)C1N(CC(=O)F)C(=O)CC(c2cccc(Cl)c2)C12C(=O)Nc1cc(Cl)ccc12
Reactant: CS(=O)(=O)N1CCC(N)CC1
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Solvent: CN1CCOCC1
Product: C=C(C)C1N(CC(=O)NC2CCN(S(C)(=O)=O)CC2)C(=O)CC(c2cccc(Cl)c2)C12C(=O)Nc1cc(Cl)ccc12
Yield: 34.3 %

Procedure:
In a manner similar to the method described in example 34b, racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-1′-fluorocarbonylmethyl-2′-isopropenylspiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (0.2 g, 0.433 mmol) prepared in example 116d was reacted with 1-methylsulfonyl-piperidin-4-yl-amine (0.15 g, 0.86 mmol), N-methylmorpholine (90 mg, 0.86 mmol) and 4-dimethylaminopyridine (5 mg) in tetrahydrofuran to give racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-isopropenyl-1′-[(1-methylsulfonyl-piperidin-4-yl)aminocarbonyl-methyl]spiro[3H-indole-3,3′ piperidine]-2,6′(1H)-dione as an off-white solid (Yield: 92 mg, 38.3%).
Reaction SMILES: [O:1]([CH2:8][CH2:9][CH2:10][CH2:11]Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:13][C:14]1[CH:19]=[CH:18][C:17]([C:20](=[O:22])[CH3:21])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[O:1]([CH2:8][CH2:9][CH2:10][CH2:11][O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20](=[O:22])[CH3:21])=[CH:16][CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: BrCCCCOc1ccccc1
Reactant: CC(=O)c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(=O)c1ccc(OCCCCOc2ccccc2)cc1

Procedure:
A mixture 100 grams (0.438 mole) of 4-phenoxybutyl bromide, 59.5 grams (0.438 mole) of p-hydroxyacetophenone, and 60.4 grams (0.438 mole) of potassium carbonate in approximately 200 milliliters of dry dimethylformamide, is stirred at its reflux temperature for a period of about 4 hours. The reaction mixture is cooled, water added, and the reaction product removed by filtration. The product is washed with a solution of 2 N sodium hydroxide, washed with water, and recrystallized twice from isopropyl alcohol to yield the desired p-(4-phenoxybutoxy) acetophenone having a m.p. of 104°-6° C.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C:23]([C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)=[CH:22][N:21]([CH2:30][CH2:31][OH:32])[N:20]=2)=[CH:15][CH:14]=1.N1C=CC=CC=1.[CH3:39][S:40](Cl)(=[O:42])=[O:41]>C(Cl)Cl>[CH3:39][S:40]([O:32][CH2:31][CH2:30][N:21]1[CH:22]=[C:23]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=2)[C:19]([C:16]2[CH:15]=[CH:14][C:13]([O:12][CH2:11][C:2]3[CH:3]=[CH:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][N:6]=4)[N:1]=3)=[CH:18][CH:17]=2)=[N:20]1)(=[O:42])=[O:41]
Reactant: OCCn1cc(-c2ccncc2)c(-c2ccc(OCc3ccc4ncccc4n3)cc2)n1
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CS(=O)(=O)OCCn1cc(-c2ccncc2)c(-c2ccc(OCc3ccc4ncccc4n3)cc2)n1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A stirred solution of Intermediate 5B, 2-(3-(4-((1,5-naphthyridin-2-yl)methoxy)phenyl)-4-(pyridin-4-yl)-1H-pyrazol-1-yl)ethanol in DCM is cooled at 0° C. Pyridine (12 equivalents) and methanesulfonyl chloride (8 equivalents) are added and the reaction mixture is stirred at 0° C. for 1 h. The mixture is quenched with water and extracted with more DCM. The organic solvent is separated, dried (MgSO4), and concentrated under reduced pressure. The crude residue is purified by silica gel column chromatography. The desired fractions are collected and concentrated under reduced pressure to yield 2-(3-(4-((1,5-naphthyridin-2-yl)methoxy)phenyl)-4-(pyridin-4-yl)-1H-pyrazol-1-yl)ethyl methanesulfonate.
Reaction SMILES: C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(C(C)C)CC)(C)C.[OH:25][C@@H:26]([C@H:28]1[C:49](=[O:50])[N:30]2[CH:31]([C:36]([O:38][CH2:39][C:40]3[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][CH:41]=3)=[O:37])[C:32](=O)[C@H:33]([CH3:34])[C@H:29]12)[CH3:27].[OH:51][CH2:52][CH2:53][N:54]1[CH2:59][CH2:58][N:57]([C:60]([C@@H:62]2[CH2:66][C@H:65]([SH:67])[CH2:64][N:63]2[C:68]([O:70][CH2:71][C:72]2[CH:77]=[CH:76][C:75]([N+:78]([O-:80])=[O:79])=[CH:74][CH:73]=2)=[O:69])=[O:61])[CH2:56][CH2:55]1>C(#N)C>[OH:51][CH2:52][CH2:53][N:54]1[CH2:55][CH2:56][N:57]([C:60]([C@@H:62]2[CH2:66][C@H:65]([S:67][C:32]3[C@H:33]([CH3:34])[C@@H:29]4[C@@H:28]([C@H:26]([OH:25])[CH3:27])[C:49](=[O:50])[N:30]4[C:31]=3[C:36]([O:38][CH2:39][C:40]3[CH:41]=[CH:42][C:43]([N+:46]([O-:48])=[O:47])=[CH:44][CH:45]=3)=[O:37])[CH2:64][N:63]2[C:68]([O:70][CH2:71][C:72]2[CH:73]=[CH:74][C:75]([N+:78]([O-:80])=[O:79])=[CH:76][CH:77]=2)=[O:69])=[O:61])[CH2:58][CH2:59]1
Reactant: O=C([C@@H]1C[C@H](S)CN1C(=O)OCc1ccc([N+](=O)[O-])cc1)N1CCN(CCO)CC1
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)C(=O)[C@H](C)[C@H]12
Agent: O=P(Cl)(c1ccccc1)c1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](C(=O)N4CCN(CCO)CC4)N(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)[C@H](C)[C@H]12
Reaction time: 1 h
Yield: 52.5 %

Procedure:
1.82 ml of diphenylphosphoryl chloride and 1.54 ml of diisopropylethylamine were added dropwise, whilst ice-cooling, to a solution of 3.0 g of 4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 38 ml of dry acetonitrile, and the resulting mixture was stirred at the same temperature for 1 hour. 1.54 ml of diisopropylethylamine and a solution of 3.63 g of (2S,4S)-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-4-mercapto-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (prepared as described in Preparation 54) in 30 ml of dry acetonitrile were then simultaneously added dropwise to the mixture, whilst ice-cooling, and the resulting mixture was stirred at the same temperature for 3 hours, after which it was allowed to stand overnight in a refrigerator. At the end of this time, the reaction mixture was worked up in a similar manner to that described in Example 49(b). The crude product was then purified by column chromatography through silica gel, using a 2:1 by volume mixture of ethyl acetate and methanol as the eluent, to give 3.4 g of the title compound, as a powder. The infrared absorption spectrum and nuclear magnetic resonance spectrum of the product were identical with those of the compound prepared as described in step 54(i), above.
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[CH:13]=[CH:12][C:11](I)=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16])([CH3:4])([CH3:3])[CH3:2].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.Br[C:38]1[CH:43]=[CH:42][N:41]=[CH:40][CH:39]=1>>[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:38]2[CH:43]=[CH:42][N:41]=[CH:40][CH:39]=2)=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16])([CH3:4])([CH3:3])[CH3:2]
Reactant: Brc1ccncc1
Reactant: CC(C)(C)OC(=O)Nc1ccc(I)cc1[N+](=O)[O-]
Agent: CC1(C)OB(B2OC(C)(C)C(C)(C)O2)OC1(C)C
Product: CC(C)(C)OC(=O)Nc1ccc(-c2ccncc2)cc1[N+](=O)[O-]

Procedure:
Prepared from (4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example A1), bis(pinacolato)diboron and 4-bromopyridine according to the general procedure C. Obtained as a yellow solid (379 mg).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[C:9]12(O)[CH2:18][CH:13]3[CH2:14][CH:15]([CH2:17][CH:11]([CH2:12]3)[CH2:10]1)[CH2:16]2.S(=O)(=O)(O)O>ClCCl>[C:9]12([C:6]3[CH:7]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=3[OH:8])[CH2:18][CH:13]3[CH2:14][CH:15]([CH2:17][CH:11]([CH2:12]3)[CH2:10]1)[CH2:16]2
Reactant: OC12CC3CC(CC(C3)C1)C2
Reactant: Oc1ccc(Br)cc1
Agent: O=S(=O)(O)O
Solvent: ClCCl
Product: Oc1ccc(Br)cc1C12CC3CC(CC(C3)C1)C2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of 6.92 g (40.0 mmol) of 4-bromophenol and 6.08 g (40.0 mmol) of 1-adamantanol in 20 ml of dichloromethane (anhydrous) was added 2.0 ml of conc. sulfuric acid over a span of 2 minutes. The solution became orange in color and a white precipitate was formed. The solution was allowed to stir at room temperature for 8 hours, partitioned between 250 ml of water and 100 ml of ethyl ether, diluted with approximately 60 ml of sat. aqueous NaHCO3 solution and allowed to stir at room temperature. The layers were separated and the aqueous phase was washed with 3×75 ml-portions of dichloromethane. All organic phases were combined, dried over MgSO4, filtered and concentrated in vacuo to yield a yellow solid. Purification by flash chromatography (silica, 10% ethyl acetate in hexane) yielded the title compound as a light yellow solid. PMR (CDCl3): d 1.77 (6H, s), 2.08 (9H, s), 4.76 (1H, s), 6.53 (1H, d, J=8.4 Hz), 7.14 (1H, dd, J=8.4, 2.4 Hz), 7.29 (1H, d, J=2.4 Hz).
Reaction SMILES: CSC.S([O:9][CH3:10])(OC)(=O)=O.[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][C:20]([C:22]2([Cl:25])[CH2:24][CH2:23]2)=O)=[CH:14][CH:13]=1.[OH-].[K+].OO>C(O)(C)(C)C>[Cl:25][C:22]1([C:20]2([CH2:19][CH2:18][C:15]3[CH:14]=[CH:13][C:12]([Cl:11])=[CH:17][CH:16]=3)[CH2:10][O:9]2)[CH2:23][CH2:24]1
Reactant: COS(=O)(=O)OC
Reactant: O=C(CCc1ccc(Cl)cc1)C1(Cl)CC1
Agent: OO
Agent: [K+]
Agent: [OH-]
Solvent: CSC
Solvent: CC(C)(C)O
Product: Clc1ccc(CCC2(C3(Cl)CC3)CO2)cc1
Temperature: 30 °C
Reaction time: 14 h
Yield: 74.4 %

Procedure:
16 ml (0.22 mol) of dimethyl sulphide and 24.2 g (0.19 mol) of dimethyl sulphate are added to 30 ml of tert.-butanol and the mixture is allowed to stand for 14 hours at 20° C. A solution of 17 g (0.07 mol) of 1-chlorocyclopropyl 4-chlorophenylethyl ketone in 70 ml of tert.-butanol is initially added dropwise with stirring to the reaction mixture and 22 g of potassium hydroxide powder are then introduced, the temperature of the reaction mixture being held at 20° to 30° C. The mixture is stirred for a further 3 hours at 30° C., then the dimethyl sulphide is stripped off under reduced pressure and the reaction mixture is then poured into 50 ml of a 1% strength aqueous hydrogen peroxide solution. The mixture is extracted using ethyl acetate. The organic phase is washed using water and is concentrated by stripping off the solvent under reduced pressure after drying over sodium sulphate. In this manner, 13.4 g (75% of theory) of 2-(1-chlorocyclopropyl)-2-(4-chlorophenylethyl)-oxirane are obtained in the form of an oily product, which is further reacted without additional purification. ##STR68##
Reaction SMILES: [C:1](#[N:4])[CH:2]=[CH2:3].[OH2:5]>>[C:1](#[N:4])[CH:2]=[CH2:3].[C:1]([NH2:4])(=[O:5])[CH:2]=[CH2:3]
Reactant: O
Solvent: C=CC#N
Product: C=CC(N)=O
Yield: 87.9 %

Procedure:
One gram of the catalyst prepared was reacted with 5 grams of a 7% solution of acrylonitrile in water at 135° C. for 1 hour to give a 72.5% conversion of acrylonitrile with an 87.9% yield of acrylamide based on the amount of acrylonitrile consumed.
Reaction SMILES: [CH2:1]([OH:7])[CH2:2][CH2:3][CH2:4][C:5]#[CH:6].[Cl:8][C:9]1[CH:14]=[CH:13][C:12](I)=[CH:11][CH:10]=1>>[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:6]#[C:5][CH2:4][CH2:3][CH2:2][CH2:1][OH:7])=[CH:11][CH:10]=1
Reactant: Clc1ccc(I)cc1
Reactant: C#CCCCCO
Product: OCCCCC#Cc1ccc(Cl)cc1

Procedure:
In a manner described in Example 18 above, 5-hexyn-1-ol was reacted with 1-chloro-4-iodobenzene to give the title compound, MS m/Z exact mass 209.724 (M+H)(calcd. For C12H13OCl 209.70).
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:16])[CH2:11][C:12](=[O:15])[CH2:13][CH3:14])=[CH:5][CH:4]=1.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.[H][H]>CO.O>[F:1][C:2]([F:17])([F:18])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:16])[CH2:11][C@@H:12]([OH:15])[CH2:13][CH3:14])=[CH:5][CH:4]=1
Reactant: CCC(=O)CC(=O)Nc1ccc(C(F)(F)F)cc1
Reactant: [H][H]
Agent: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: O
Solvent: CO
Product: CC[C@H](O)CC(=O)Nc1ccc(C(F)(F)F)cc1
Temperature: 60 °C
Yield: 95 %

Procedure:
N-[4-(trifluoromethyl)phenyl]-3-oxopentanoic acid amide 1.30 g (5.0 mmol) produced in Example 1 and ((S)-BINAP)RuBr2 50.0 mg (0.057 mmol) (BINAP denotes 2,2′-bisdiphenylphosphino-1,1′-binaphthyl. It was prepared according to the method described in Tetrahedron Asymmetry, 1994,5,675) were mixed with 20 mL of a methanol-water (10/1 in volume) solution. Hydrogen replacement was carried out three times and after the reaction solution was heated to 60° C., reaction was carried out under hydrogen pressure (3.0 kg/cm2) for 12 hours. After releasing hydrogen, the solution was concentrated under reduced pressure and purifying on silica gel chromatography was carried out to obtain (S)-N-[4-(trifluoromethyl)phenyl]-3-hydroxypentanoic acid amide as a white solid (1.23 g, isolated yield: 95%). The optical purity of the product was determined by HPLC analysis (column; Daicel Chiral Pack AD-H 4.6×250 mm: eluent; hexane/isopropanol=90/10: flow rate; 1.0 mL/min: column temperature; 30° C.: detector; UV 210 nm: retention time; (S) antipode=12.0 minutes, (R) antipode=9.3 minutes) to be 84.7% ee. 1H-NMR (CDCl3, 400 MHz/ppm): δ 1.00 (3H, t), 1.5-1.7 (2H, br), 2.50 (1H, dd), 2.59 (1H, dd), 2.75 (br, 1H), 4.06 (1H, m), 7.57 (2H, d), 7.64 (2H, d), 8.21 (1H, br)
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:24])[CH2:9][CH2:10][CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[CH:4][CH:3]=1.CN1CCOCC1>[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC.C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:24])[CH2:9][CH2:10][CH:11]2[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:15][CH2:16]2)=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CCC(CCC(O)c2ccc(F)cc2)CC1
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(CCC(=O)c2ccc(F)cc2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 76.7 %

Procedure:
A mixture of 500 mg (1.5 mmol) of 4-(3-(4-fluorophenyl)-3-(RS)-hydroxypropyl)-1-(t-butoxycarbonyl) piperidine (from EXAMPLE 188, Step B), 351 mg (3.0 mmol) of 4-(methyl)morpholine and 800 mg of 4 A molecular sieves in 10 _mL of CH2Cl2 at 0° C. was treated with 35 mg (0.1 mmol) of tetrapropylammonium perruthenate. The cooling bath was removed and the mixture was stirred at rt for 1 h. The mixture was filtered and the filtrate was concentrated. Flash chromatography on 15 g of silica gel using 3:1 v/v hexanes/ether afforded 386 mg (78%) of the title compound: 1H NMR (500 MHz, CDCl3) δ 1.10-1.19 (m, 2H), 1.43-1.49 (m, 1H), 1.45 (s, 9H), 1.58-1.70 (4H), 2.65-2.70 (m, 2H), 2.70 (t, J=7.5, 2H), 4.054.1 1 (m, 2H), 7.11-7.15 (m, 21), 7.97-8.00 (m, 2H).
Reaction SMILES: [OH:1][C@@H:2]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:12]=[C:13]([NH:17][C:18](=[O:22])[CH:19]([CH3:21])[CH3:20])[CH:14]=[CH:15][CH:16]=2)[CH2:7][CH2:6]1.[CH3:29][O:30][C:31]1[CH:32]=[C:33](O)[CH:34]=[CH:35][CH:36]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.N>C1COCC1.C(Cl)(Cl)Cl>[CH3:29][O:30][C:31]1[CH:36]=[C:35]([CH:34]=[CH:33][CH:32]=1)[O:1][C@H:2]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:12]=[C:13]([NH:17][C:18](=[O:22])[CH:19]([CH3:21])[CH3:20])[CH:14]=[CH:15][CH:16]=2)[CH2:7][CH2:6]1
Reactant: COc1cccc(O)c1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CC[C@@H](O)c3ccccc3)CC2)c1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: N
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: ClC(Cl)Cl
Product: COc1cccc(O[C@@H](CCN2CCC(c3cccc(NC(=O)C(C)C)c3)CC2)c2ccccc2)c1
Temperature: 25 °C
Reaction time: 72 h
Yield: 46.5 %

Procedure:
A mixture of N-(3-{1-[(3R)-3-hydroxy-3-phenylpropyl]-4-piperidinyl}phenyl)-2-methylpropanamide (5.20 mg, 0.0137 mmol), 3-methoxyphenol (100 mg), triphenylphosphine (30.0 mg, 0.115 mmol) and diethyl azodicarboxylate (7.42 mg, 0.0426 mmol) in THF (0.50 mL) was stirred at room temperature for 3 days. Chromatography using silica preparative TLC plates [2.5% of NH3 (2.0 M in methanol) in CHCl3] gave the desired product (3.1 mg, 46.6% yield) as a thick oil: 1HNMR (400 MHz, CDCl3) δ 7.47 (d, 1H, J=6.7 Hz), 7.42 (s, 1H), 7.3–7.20 (m, 3H), 7.20 (m, 3H), 7.07 (t, 1H, J=8.4 Hz), 6.97 (apparent d, 1H, J=6.7 Hz), 6.40 (m, 3H), 5.27 (apparent dd, 1H, J=5.3, 8.0 Hz), 3.74 (s, 3H), 3.38 (m, 2H), 2.93 (m, 2H), 2.61 (s, 1H), 2.53 (apparent sept, partially hidden, 1H, J=6.5 Hz), 2.30–2.10 (m, 6H), 1.82 (m, 2H), 1.25 (d, 6H, J=6.9 Hz); ESMS m/e: 487.3 (M+H)+.