Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10](Cl)(=[O:12])=[O:11])([O-:3])=[O:2].[NH2:14][CH2:15][C@H:16]1[CH2:21][CH2:20][C@H:19]([C:22]([OH:24])=[O:23])[CH2:18][CH2:17]1>O1CCOCC1.[OH-].[Na+]>[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([NH:14][CH2:15][C@H:16]1[CH2:17][CH2:18][C@H:19]([C:22]([OH:24])=[O:23])[CH2:20][CH2:21]1)(=[O:12])=[O:11])([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)Cl
Reactant: NC[C@H]1CC[C@H](C(=O)O)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: O=C(O)[C@H]1CC[C@H](CNS(=O)(=O)c2ccccc2[N+](=O)[O-])CC1
Reaction time: 0.5 h

Procedure:
A solution of 29.9 g (0.135 mol) of o-nitrobenzenesulfonyl chloride in 150 ml of dioxane and 150 ml of 1 N NaOH was added simultaneously and dropwise at 4° C. (ice bath) to a solution of 14.13 g (0.09 mol) of trans-4-(aminomethyl)cyclohexanecarboxylic acid in a two-phase system comprising 90 ml of 1 N NaOH and 90 ml of dioxane. After the slightly exothermic reaction had died down, stirring was carried out for 30 minutes at room temperature, the precipitate which separated out was filtered off with suction and washed with a little ice water and the filtrate was evaporated down under reduced pressure, further precipitation of salt occurring. The combined amounts of salt were digested with ether, suspended in water, acidified with 1 M KHSO4 solution and extracted with ethyl acetate. The ethyl acetate phase was washed with sodium chloride solution, dried over Na2SO4 and evaporated down under reduced pressure.
Reaction SMILES: [F:1][C@H:2]1[CH2:19][C@@:17]2([CH3:18])[C@@H:13]([CH2:14][CH2:15][C@@H:16]2[OH:20])[C@H:12]2[C@H:3]1[C@@H:4]1[C:9]([CH2:10][C@H:11]2[CH3:21])=[CH:8][C:7](=[O:22])[CH2:6][CH2:5]1.[C:23](Cl)(=[O:30])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].C(=O)(O)[O-].[Na+]>O1CCCC1.N1C=CC=CC=1>[F:1][C@H:2]1[CH2:19][C@@:17]2([CH3:18])[C@@H:13]([CH2:14][CH2:15][C@@H:16]2[O:20][C:23](=[O:30])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[C@H:12]2[C@H:3]1[C@@H:4]1[C:9]([CH2:10][C@H:11]2[CH3:21])=[CH:8][C:7](=[O:22])[CH2:6][CH2:5]1
Reactant: C[C@@H]1CC2=CC(=O)CC[C@@H]2[C@@H]2[C@@H]1[C@@H]1CC[C@H](O)[C@@]1(C)C[C@@H]2F
Reactant: CCCCCCC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: CCCCCCC(=O)O[C@H]1CC[C@H]2[C@H]3[C@H]([C@@H](F)C[C@]12C)[C@H]1CCC(=O)C=C1C[C@H]3C
Reaction time: 1 h

Procedure:
A solution of 220 mg of 11β-fluoro-17β-hydroxy-7α-methylestr-4-ene-3-one (I) in 5 ml of tetrahydrofuran and 1.09 ml of pyridine was mixed drop by drop at 0° C. with 1.09 ml of heptanoyl chloride and stirred for 1 hour. Then, it was mixed with sodium bicarbonate solution, extracted three times with ethyl acetate, washed neutral, dried on sodium sulfate, concentrated by evaporation in a vacuum and chromatographed on silica gel with hexane/ethyl acetate. 210 mg of pure 11β-fluoro-17β-heptanoyloxy-7α-methylestr-4-en-3-one (I′) was obtained as a foam ([α]D20=+40.8° (c=0.56% in chloroform)).
Reaction SMILES: C([O:5][C:6](=[O:18])[C:7]1[CH:12]=[C:11]([CH2:13][CH:14]([CH3:16])[CH3:15])[C:10]([CH3:17])=[N:9][CH:8]=1)(C)(C)C.[ClH:19]>O1CCOCC1>[ClH:19].[CH2:13]([C:11]1[C:10]([CH3:17])=[N:9][CH:8]=[C:7]([CH:12]=1)[C:6]([OH:18])=[O:5])[CH:14]([CH3:16])[CH3:15]
Reactant: Cc1ncc(C(=O)OC(C)(C)C)cc1CC(C)C
Agent: Cl
Solvent: C1COCCO1
Product: Cc1ncc(C(=O)O)cc1CC(C)C
Reaction time: 3 h

Procedure:
To a solution of 6-methyl-5-isobutyl-nicotinic acid tert.-butyl ester (0.50 g, 2 mmol) in dioxane (20 mL), 4 N HCl in dioxane (30 mL) is added. The mixture is stirred for 3 h. The solvent is evaporated to give 5-isobutyl-6-methyl-nicotinic acid hydrochloride (0.52 g); LC-MS: tR=0.54 min; [M+1]+=194.29; 1H NMR (D6-DMSO) δ 0.91 (d, J=6.5 Hz, 6H), 1.91 (hept, J=6.5 Hz), 2.68 (d, J=7.3 Hz, 2H), 2.73 (s, 3H), 8.47 (d, J=1.8 Hz, 1H), 8.90 (d, J=2.0 Hz, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4]Br.[F:10][C:11]1[CH:19]=[CH:18][C:14]([C:15](Cl)=[O:16])=[CH:13][CH:12]=1.FC1C=CC=CC=1CBr.C1(C(Cl)=O)CCC1>>[F:10][C:11]1[CH:19]=[CH:18][C:14]([C:15]([CH2:4][C:3]2[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=2[Cl:1])=[O:16])=[CH:13][CH:12]=1
Reactant: Clc1ccccc1CBr
Reactant: O=C(Cl)c1ccc(F)cc1
Agent: Fc1ccccc1CBr
Agent: O=C(Cl)C1CCC1
Product: O=C(Cc1ccccc1Cl)c1ccc(F)cc1
Yield: 34 %

Procedure:
Following a procedure similar to that described in Preparation 13, except that equivalent amounts of 2-chlorobenzyl bromide and 4-fluorobenzoyl chloride were used in place of the 2-fluorobenzyl bromide and cyclobutanecarbonyl chloride, the title compound was obtained as a colorless powder in a yield of 34%.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C:12](=[NH:16])OCC)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][NH2:23]>C1(C)C=CC=CC=1>[NH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:12]([NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])=[NH:16]
Reactant: NCCCCCN
Reactant: CCOC(=N)NC(=O)OCc1ccccc1
Solvent: Cc1ccccc1
Product: N=C(NCCCCCN)NC(=O)OCc1ccccc1
Temperature: 40 °C
Reaction time: 48 h

Procedure:
A mixture of N-benzyloxycarbonyl-O-methyl-isourea (II-OMe) (0.42 g, 2.0 mmol), toluene (3.5 mL) and 1,5-diaminopentane (0.50, 5.0 mmol) was stirred at 40° C. and for 48 h. The reaction mixture was concentrated under vacuum (35° C., 0.3 mbar) to give a crude product which was crystallized by addition of toluene followed by additon of heptane. The yield of N-(5-aminopentyl)-N'-benzyloxycarbonyl guanidine (IIId) was 0.3 g (60% in theory).
Reaction SMILES: [SH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.[H-].[Na+].Cl[CH:15]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[O:28][CH3:29])[CH2:16][N:17]1[CH:21]=[CH:20][N:19]=[CH:18]1>CN(C)C=O>[CH3:29][O:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[CH:15]([S:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:10][CH:11]=1)[CH2:16][N:17]1[CH:21]=[CH:20][N:19]=[CH:18]1
Reactant: COC(=O)c1ccc(S)cc1
Reactant: COc1ccccc1C(Cl)Cn1ccnc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(SC(Cn2ccnc2)c2ccccc2OC)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 69.2 %

Procedure:
915 mg of methyl 4-mercaptobenzoate were dissolved in 6 ml of dry dimethylformamide, and 237 mg of a 55% w/w suspension of sodium hydride in mineral oil were added, whilst ice-cooling, to the resulting solution, followed by stirring at room temperature for 30 minutes. A solution of 1.17 g of 1-[2-chloro-2-(2-methoxyphenyl)ethyl]imidazole dissolved in 6 ml of dry dimethylformamide was added to the resulting solution. At the end of this time, the resulting mixture was treated and purified similarly to the procedure described in Example 1, to give 1.26 g of the title compound as an oil.
Reaction SMILES: S(Cl)(Cl)=O.[N+:5]([C:8]1[CH:16]=[C:12]([C:13]([OH:15])=[O:14])[C:11]([OH:17])=[CH:10][CH:9]=1)([O-:7])=[O:6].[CH3:18]O>>[CH3:18][O:14][C:13](=[O:15])[C:12]1[CH:16]=[C:8]([N+:5]([O-:7])=[O:6])[CH:9]=[CH:10][C:11]=1[OH:17]
Reactant: CO
Reactant: O=C(O)c1cc([N+](=O)[O-])ccc1O
Solvent: O=S(Cl)Cl
Product: COC(=O)c1cc([N+](=O)[O-])ccc1O

Procedure:
Thionyl chloride (30 ml) was added dropwise to a solution of 5-nitro salicyclic acid (25 g) in methanol (300 ml) over 30 minutes. After stirring at room temperature for 18 hours the solvent and excess thionyl chloride was removed on a rotary evaporator. The residue was dissolved in hot toluene, filtered and cooled. A white solid methyl-2-hydroxy-5-nitro-benzoate was isolated by filtration. This material was treated with acetic anhydride (20 ml) and sulfuric acid (8 drops) at 50° C. for 1 hour. The reaction was cooled, poured into cold water (250 ml), stirred for 30 minutes and the title compound was isolated by vacuum filtration. This material was washed well with water, m.p. ca. 70°-72° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14]Br)[CH:6]=1.[C:17]1([CH:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:24][NH2:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CS(C)=O.O>[CH3:1][O:2][C:3](=[O:16])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][NH:25][CH2:24][CH:23]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:6]=1
Reactant: COC(=O)Cc1cccc(OCCCBr)c1
Reactant: NCC(c1ccccc1)c1ccccc1
Solvent: O
Solvent: CS(C)=O
Product: COC(=O)Cc1cccc(OCCCNCC(c2ccccc2)c2ccccc2)c1
Yield: 96.3 %

Procedure:
A solution of [3-(3-bromo-propoxy)-phenyl]-acetic acid methyl ester (2) (2.0 g, 0.007 mol) and 2,2-diphenylethylamine (2.5 g, 0.013 mol) in DMSO (5 mL) was stirred at room temperature for 18 hours. The reaction mixture was diluted with water (30 mL) and extracted with EtOAc (3×25 mL). The combined organic extracts were washed with brine (15 mL), dried over Na2SO4, concentrated to an oil, which was purified by flash chromatography (9:1 CH2Cl2/MeOH) to give the desired product as oil 2.72 g in 96% yield. 1H NMR (CDCl3) δ 7.24 (m, 7H), 7.19 (t, 3H), 6.85 (d, 1H), 6.74 (s, 1H), 6.72 (d, 2H), 5.26 (s, 1H), 4.22 (t, 1H), 3.96 (t, 2H), 3.68 (s, 3H), 3.57 (d, 2H), 3.26 (d, 2H), 2.84 (t, 2H), 1.92 (m, 2H). 13C NMR (CDCl3) δ 173.3, 160.5, 144.4, 136.7, 130.9, 130.1, 129.5, 129.4, 127.9, 122.9, 116.9, 114.6, 67.6, 56.0, 53.5, 52.6, 48.3, 42.6, 31.0.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[S:11]([CH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)(=[O:13])=[O:12].Cl[C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][N:22]=1>>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[S:11]([CH:14]1[CH2:19][CH2:18][N:17]([C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][N:22]=2)[CH2:16][CH2:15]1)(=[O:12])=[O:13]
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Reactant: O=S(=O)(c1ccc2ccccc2c1)C1CCNCC1
Product: O=[N+]([O-])c1ccc(N2CCC(S(=O)(=O)c3ccc4ccccc4c3)CC2)nc1
Yield: 31.1 %

Procedure:
Using the procedure from Example 7A, Step 7E, 4-(2-naphthylsulfonyl)piperidine (Example 11, Step 3, 130 mg, 0.51 mmol) was reacted with 2-chloro-5-nitropyridine (158 mg, 1.0 mmol) to afford the title compound (63 mg), a yellow solid, in 31% yield.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][S@](C(C)(C)C)=O)[CH3:9])=[CH:4][CH:3]=1.[ClH:17]>CO>[ClH:17].[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH2:10])[CH3:9])=[CH:4][CH:3]=1
Reactant: C[C@H](N[S@@](=O)C(C)(C)C)c1ccc(Br)cc1
Agent: Cl
Solvent: CO
Product: C[C@H](N)c1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
(S)—N—((S)-1-(4-bromophenyl)ethyl)-2-methylpropane-2-sulfinamide (170 mg, 0.56 mmol) was dissolved in methanol (2 mL) followed by addition of con.HCl (1 mL). The mixture was stirred at RT for 4 h and then was concentrated and evaporated with toluene twice to afford the titled compound.
Reaction SMILES: O[CH:2]=[C:3]1[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]1=O.Cl.[C:14]1([NH:20][NH2:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Cl>C(O)C>[C:14]1([N:20]2[C:4]3[C:5]4[C:10]([CH2:11][C:3]=3[CH:2]=[N:21]2)=[CH:9][CH:8]=[CH:7][CH:6]=4)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: NNc1ccccc1
Reactant: O=C1C(=CO)Cc2ccccc21
Agent: Cl
Solvent: CCO
Product: c1ccc(-n2ncc3c2-c2ccccc2C3)cc1

Procedure:
2-Hydroxymethlene indan-1-one (Example 1(ii)(a) (6.0 g, 37.5 mmol), phenylhydrazine hydrochloride (Aldrich) (5.48 g, 37.9 mmol), 10 M hydrochloric acid (1 cm3) and ethanol (30 cm3) were stirred under reflux for 19 hours. After cooling, the solvent was evaporated under reduced pressure and the residue dissolved in dichloromethane, then washed with 2M sodium hydroxide. The organic layer was separated, dried (Na2SO4) filtered and concentrated in vacuo. Purification by Kugelrohr distillation afforded an off-white solid (150° C., 0.01 mmHg) m.p. 119-120° C.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4][CH2:3]1.[H-].[Na+].Br[CH2:12][C:13]#[CH:14]>C1COCC1>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([O:8][CH2:14][C:13]#[CH:12])[CH2:4][CH2:3]1
Reactant: CN1CCC(O)CC1
Reactant: C#CCBr
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: C#CCOC1CCN(C)CC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 9.1 %

Procedure:
A solution of 1-methylpiperidin-4-ol (1.15 g, 10.0 mmol) in dry THF (5 mL) was added drop wise to a suspension of NaH (60% dispersion in mineral oil, 0.400 g, 10.0 mmol) in dry THF (5 mL) at 0° C. The reaction was kept at the same temperature for 15 min then stirred at room temperature for 1 h. 3-Bromoprop-1-yne (0.75 mL, 10.0 mmol), was slowly added and the mixture was stirred at room temperature for 16 h. After solvent removal, the residue was taken up with DCM (50 mL), washed with water (50 mL), dried over sodium sulfate and purified by flash chromatography on silica gel (DCM/MeOH/TEA 90/10/0.1) to afford the title compound (0.140 g, 9%).
Reaction SMILES: [OH-].[K+].[Cl:3][C:4]1[CH:5]=[C:6]([C:16](=[O:25])[CH:17]([NH:19][C:20](=[O:24])[O:21][CH2:22][CH3:23])[CH3:18])[CH:7]=[CH:8][C:9]=1[O:10]C(OCC)=O>O.CO>[Cl:3][C:4]1[CH:5]=[C:6]([C:16](=[O:25])[CH:17]([NH:19][C:20](=[O:24])[O:21][CH2:22][CH3:23])[CH3:18])[CH:7]=[CH:8][C:9]=1[OH:10]
Reactant: CCOC(=O)NC(C)C(=O)c1ccc(OC(=O)OCC)c(Cl)c1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CCOC(=O)NC(C)C(=O)c1ccc(O)c(Cl)c1
Reaction time: 0.33 h
Yield: 71.2 %

Procedure:
A solution of 12.50 g of 85% potassium hydroxide (i.e. potassium hydroxide of purity about 85%, of which the main impurity is water) dissolved in a mixture of 20 ml of water and 30 ml of methanol was added dropwise, whilst ice-cooling, to a solution of 10.87 g of ethyl N-[2-(3-chloro-4-ethoxycarbonyloxyphenyl)-1-methyl-2-oxoethyl]carbamate [prepared as described in step (a) above] in 130 ml of methanol over a period of 5 minutes. The mixture was then stireed at room temperature for 20 minutes. At the end of this time, the mixture was concentrated by evaporation under reduced pressure and then acidified with 5% w/v aqueous hydrochloric acid. It was then extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried. The ethyl acetate of the solvent was then removed by evaporation under reduced pressure. The residue was recrystallized from a mixure of ethyl acetate and hexane, to give 6.12 g of the title compound as a yellowish-brown powder melting at 106°-108° C.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19](O)=[O:20])[CH:5]=[CH:6][CH:7]=1.B.C1COCC1>C1COCC1>[I:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][OH:20])[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)CCCCCCCCCCCc1cccc(I)c1
Agent: B
Solvent: C1CCOC1
Product: OCCCCCCCCCCCCc1cccc(I)c1
Temperature: 25 °C
Reaction time: 20 h
Yield: 98.5 %

Procedure:
Anhydrous THF (20 ml) was added to a flame-dried 100 ml two-necked flask contain 12-m-iodophenyldodecanoic acid (3.30 g, 8.21 mmol). The solution was cooled in an ice bath before BH3THF (15.0 ml, 1 M) was added dropwise. The reaction mixture was allowed to warm to room temperature and to stir under anhydrous conditions for 20 hours. The reaction mixture was again cooled to 0° C. and quenched with H2O. Ether and additional H2O were then added. The ether layer was extracted with H2O, sat. NaHCO3, and more H2O and dried (MgSO4). The solvent was removed under reduced pressure to yield a yellow oil. The crude compound was purified by column chromatography (90 g silica gel, hexanes:ethyl acetate 8:1) to yield a white solid, compound 8, 12-m-iodophenyldodecanol (3.14 g, 98.4% yield).
Reaction SMILES: [CH3:1][C:2]([NH:11][C:12](=[O:15])[CH2:13][CH3:14])([CH3:10])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[N+:16]([O-])([O-:18])=[O:17].[K+]>OS(O)(=O)=O>[CH3:10][C:2]([NH:11][C:12](=[O:15])[CH2:13][CH3:14])([CH3:1])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([N+:16]([O-:18])=[O:17])=[CH:8][CH:9]=1
Reactant: CCC(=O)NC(C)(C)Cc1ccccc1
Reactant: O=[N+]([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Product: CCC(=O)NC(C)(C)Cc1ccc([N+](=O)[O-])cc1
Temperature: 0 °C
Yield: 55 %

Procedure:
To H2SO4(20 ml) at 0-10° C. N-(1,1-dimethyl-2-phenyl-ethyl)-propionamide was slowly added. The mixture was stirred until a clear solution was obtained. Then KNO3 (750 mg, 7.42 mmol) was added in portions at 0-5° C. The mixture was stirred at room temperature for 16 h after which it was poured into ice water. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with NaOH, water and brine, dried over MgSO4, filtered, and the solvent evaporated under reduced pressure to give the product as a brown oil (1 g, 55%).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][NH:4][C:5]([C:7]1([C:11]#[N:12])[CH2:10][CH2:9][CH2:8]1)=O.C1COCC1.B.C1COCC1.Cl>O.C(O)C.CC(C)=O>[NH2:12][CH2:11][C:7]1([CH2:5][NH:4][CH2:3][CH2:2][NH2:1])[CH2:10][CH2:9][CH2:8]1
Reactant: N#CC1(C(=O)NCCN)CCC1
Agent: B
Agent: Cl
Solvent: CCO
Solvent: O
Solvent: C1CCOC1
Product: NCCNCC1(CN)CCC1
Temperature: 70 °C
Yield: 50 %

Procedure:
6.37 g (0.038 mol) of 5 and 50 mL of anhydrous THF were mixed, followed by adding 300 mL of 1 M BH3-THF solution to the mixture in an ice bath (−10° C.) of liquid nitrogen and acetone under a nitrogen gas environment to form a reaction solution. The reaction solution was subjected to reaction at −5˜0° C. for 1 hour, followed by heating the reaction solution to 70° C. to allow reaction to take place for 36 hours, and evaporating to obtain a solid substance. The solid substance, 100 mL of ethanol and 10 mL of 6N HCl were mixed, refluxed for 12 hours, followed by evaporation to form yellow oil. The yellow oil was stirred in water and was mixed with HCl to adjust pH to 2 to obtain a crude product. The crude product was purified by placing in a column (3×20 cm) filled with 100 mL of AG 50 W×8 cationic exchange resin and elutriating HCl solutions having gradient concentrations, collecting an eluent fraction of gradient concentration from 3.5 N to 4.0 N, and followed by evaporating the eluent fraction to obtain 2.98 g (0.019 mol, 50%) of 6.
Reaction SMILES: [C:1]([NH:9][CH:10]1[C:16](=[O:17])[N:15]2[CH:18]([C:22]([NH:24][CH:25]3[CH2:29][C:28](=[O:30])[O:27][CH:26]3[O:31]CC3C=CC=CC=3)=[O:23])[CH2:19][CH2:20][CH2:21][N:14]2[C:13](=[O:39])[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>[Pd].CO>[C:1]([NH:9][CH:10]1[C:16](=[O:17])[N:15]2[CH:18]([C:22]([NH:24][CH:25]([CH:26]=[O:31])[CH2:29][C:28]([OH:30])=[O:27])=[O:23])[CH2:19][CH2:20][CH2:21][N:14]2[C:13](=[O:39])[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CC(NC(=O)C2CCCN3C(=O)CCC(NC(=O)c4ccccc4)C(=O)N23)C(OCc2ccccc2)O1
Agent: [Pd]
Solvent: CO
Product: O=CC(CC(=O)O)NC(=O)C1CCCN2C(=O)CCC(NC(=O)c3ccccc3)C(=O)N12
Reaction time: 6.3 h
Yield: 87.8 %

Procedure:
A mixture of 213e (2.29 g, 4.28 mmol), 10% palladium on carbon (1.8 g) and MeOH (160 ml) was stirred under H2 at atmospheric pressure for 6.3 h. After filtering and concentrating the hydrogenation was repeated with fresh catalyst (1.8 g) for 5 h. After filtering and concentrating the residue was triturated with diethyl ether, filtered and washed well with ether to give 214e as a white solid (1.67 g, 88%): mp 143-147° C.; [α]D23 −125° (c 0.2, CH3OH ). IR (KBr) 3391, 1657, 1651, 1538, 1421, 1280, 1258; 1H NMR (CD3OD) δ 7.90 (2H, m), 7.63-7.46 (3H, m), 5.25 (1H, m), 5.08-4.85 (1H, m), 4.68-4.53 (2H, m), 4.33-4.24 (1H, m), 3.62-3.44, 3.22-3.11, 2.75-2.21, 2.15-1.92, 1.73-1.66 (11H, 5 m).
Reaction SMILES: [C:1]12([C:11]3[CH:12]=[C:13]([C:19]4[CH:20]=[C:21]5[C:26](=[CH:27][CH:28]=4)[CH:25]=[C:24]([C:29]([OH:31])=[O:30])[CH:23]=[CH:22]5)[CH:14]=[CH:15][C:16]=3[CH2:17][OH:18])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[C:32](Cl)(=[O:34])[CH3:33]>N1C=CC=CC=1>[C:1]12([C:11]3[CH:12]=[C:13]([C:19]4[CH:20]=[C:21]5[C:26](=[CH:27][CH:28]=4)[CH:25]=[C:24]([C:29]([OH:31])=[O:30])[CH:23]=[CH:22]5)[CH:14]=[CH:15][C:16]=3[CH2:17][O:18][C:32](=[O:34])[CH3:33])[CH2:8][CH:7]3[CH2:9][CH:3]([CH2:4][CH:5]([CH2:6]3)[CH2:10]1)[CH2:2]2
Reactant: CC(=O)Cl
Reactant: O=C(O)c1ccc2cc(-c3ccc(CO)c(C45CC6CC(CC(C6)C4)C5)c3)ccc2c1
Solvent: c1ccncc1
Product: CC(=O)OCc1ccc(-c2ccc3cc(C(=O)O)ccc3c2)cc1C12CC3CC(CC(C3)C1)C2

Procedure:
2.42 g (5.87 mmol) of the alcohol obtained in Example 12 in 12 ml of pyridine are treated with 0.63 ml of acetyl chloride for 30 min. The reaction medium is poured into ice cold water, and extracted with ethyl acetate. The organic phase is washed with water, dried over magnesium sulphate and evaporated to give, after recrystallization from the ethyl acetate/hexane mixture, 1.67 g (63%) of a product which melts at 251° C.
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][CH:13]=1)=[O:11]>>[Br:18][C:15]1[CH:16]=[CH:17][C:12]([C:10](=[O:11])[CH:9]=[CH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:13][CH:14]=1
Reactant: CC(=O)c1ccc(Br)cc1
Reactant: O=Cc1ccccc1
Product: O=C(C=Cc1ccccc1)c1ccc(Br)cc1

Procedure:
By a procedure similar to that of example 1.59.1, starting from benzaldehyde and 4-bromoacetophenone, 1-(4-bromophenyl)-3-phenylprop-2-en-1-one was obtained as yellowish solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:9])[C:7](=[O:8])[C:5](=[O:6])[O:4][CH2:3]1.CS(N1C[C@@H](P(C2CCCCC2)C2CCCCC2)C[C@H]1CP(C1C=CC=CC=1)C1C=CC=CC=1)(=O)=O>C1C=CC=CC=1>[CH3:1][C:2]1([CH3:9])[C@@H:7]([OH:8])[C:5](=[O:6])[O:4][CH2:3]1
Reactant: CC1(C)COC(=O)C1=O
Agent: CS(=O)(=O)N1C[C@@H](P(C2CCCCC2)C2CCCCC2)C[C@H]1CP(c1ccccc1)c1ccccc1
Solvent: c1ccccc1
Product: CC1(C)COC(=O)[C@@H]1O
Yield: 95.4 %

Procedure:
To 50 ml of benzene were added 12.8 g (100 m-mol) of ketopantolactone, 1 mg (0.0025 m-mol) of rhodium 1,5-hexadiene chloride complex compound and 3.0 mg (0.0055 m-mol) of (2S,4S)-N-methanesulfonyl-4-dicyclohexylphosphino-2-diphenylphosphinomethylpyrrolidine (MSCPM) obtained in Example 1(h). An autoclave equipped with a stirrer, a pressure gauge and a thermometer was charged with the above mixture and a treatment was carried out in the same manner as described in Example 13 whereby 12.4 g (yield: 95%) of D-pantolactone was obtained. [α]D =-42.1° (optical yield: 82.5%)
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[CH:8]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[CH2:7]2.Br[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24].Cl>CN(C=O)C>[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[C:8]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:7]2
Reactant: O=C1c2ccc(F)cc2CC1c1ccc(F)cc1
Reactant: CCOC(=O)CBr
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)CC1(c2ccc(F)cc2)Cc2cc(F)ccc2C1=O
Temperature: 10 °C
Reaction time: 0.33 h
Yield: 73.8 %

Procedure:
To a solution of 0.720 g (0.018 mol) of 60% sodium hydride suspended in 50 mL DMF at 10° C. was added dropwise 4.0 g (0.0164 mol) of the product from step B dissolved in 25 mL DMF. The reaction mixture was stirred at 10° C. for 20 min. and 3.1 g (0.0164 mol) ethyl bromoacetate was added all at once. The reaction was heated at 60° C. for 15 min, cooled to room temperature, poured into 200 mL 10% HCl, extracted with ethyl acetate (3×50 mL), washed with brine (1×100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum to afford 4.0 g of a viscous oil. 1H NMR (CDCl3) δ: 1.10 (t, 3H), 3.18 (s, 2H), 3.63 (s, 2H), 4.18 (q, 2H), 6.95-7.30 (m, 6H), 7.80 (dd, 1H). IR (neat): 1720, 1676 cm-1 .