Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:11][CH3:12])[CH:10]=1)[C:5](O)=[O:6].[H-].[H-].[H-].[H-].[Li+].[Al+3].Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:11][CH3:12])[CH:10]=1)[CH2:5][OH:6]
Reactant: COc1cc(Cl)cc(C(=O)O)c1
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Product: COc1cc(Cl)cc(CO)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 86.5 %

Procedure:
To a solution of 38a (1.0 g, 5.36 mmol, 1.0 equiv.) in 30 mL of THF was added LAH (0.20 g, 5.36 mmol, 1.0 equiv.) in several portions. The mixture was stirred at room temperature for 2 h, and poured into 50 mL of 1M aqueous HCl. The aqueous layer was extracted twice with 30 mL of EtOAc. The combined EtOAc extracts were washed with 40 mL of saturated NaHCO3, 40 mL of brine, dried over Na2SO4, and evaporated in vacuo to give 0.8 g of a white solid. 1H-NMR (DMSO-d6): δ 6.93 (s, 1H), 6.87 (m, 1H), 6.85 (m, 1H), 5.32 (t, J=5.8 Hz, 1H), 4.46 (d, J=6.0 Hz, 2H), 3.76 (s, 3H).
Reaction SMILES: [F:1][C:2]([F:11])([F:10])/[CH:3]=[CH:4]/[C:5]([O:7][CH2:8][CH3:9])=[O:6].C(O)(C(F)(F)F)=O.[CH2:19]([N:26]([CH2:30][Si](C)(C)C)[CH2:27]OC)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(Cl)Cl>[CH2:19]([N:26]1[CH2:30][C@@H:3]([C:2]([F:10])([F:11])[F:1])[C@H:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CCOC(=O)/C=C/C(F)(F)F
Reactant: COCN(Cc1ccccc1)C[Si](C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)[C@@H]1CN(Cc2ccccc2)C[C@H]1C(F)(F)F
Temperature: 25 °C
Reaction time: 8 h
Yield: 78.5 %

Procedure:
To a solution of (E)-ethyl 4,4,4-trifluorobut-2-enoate (100 g, 0.6 mol) in DCM (1.8 L) was added dropwise TFA (20.52 g, 0.18 mol) at 0° C. and then N-benzyl-1-methoxy-N-((trimethylsilyl)methyl)methanamine (170.64 g, 0.72 mol) was added and the resulting mixture was stirred at rt overnight. The reaction mixture was washed with sat. aqueous NaHCO3 (two×500 mL), dried over Na2SO4 and concentrated in vacuo and the residue was purified by silica column chromatography eluted with petroleum ether/EtOAc=100:1 to give the title compound (142 g, 79% yield) as a yellow oil.
Reaction SMILES: [N+:1]([C:4]1[CH:15]=[CH:14][C:7]([CH2:8][C@@H:9]([C:11]([OH:13])=[O:12])[NH2:10])=[CH:6][CH:5]=1)([O-:3])=[O:2].[O:16]([CH2:23][C:24](Cl)=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([O-])([O-])=O.[Na+].[Na+].Cl>[OH-].[Na+].O.C(OCC)C>[O:16]([CH2:23][C:24]([NH:10][C@H:9]([C:11]([OH:13])=[O:12])[CH2:8][C:7]1[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:15][CH:14]=1)=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: N[C@@H](Cc1ccc([N+](=O)[O-])cc1)C(=O)O
Reactant: O=C(Cl)COc1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Product: O=C(COc1ccccc1)N[C@@H](Cc1ccc([N+](=O)[O-])cc1)C(=O)O
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
4-Nitro-L-phenylalanine (21 g) was dissolved in 10% NaOH (10 ml), and an ethyl ether solution of phenoxyacetyl chloride (1.7 g) and an aqueous Na2CO3 solution prepared from Na2CO3 2.7 g and water 25 ml were alternately added stepwise thereto while stirring at room temperature over 20 minutes. After that, the mixture was stirred at a room temperature for 3 hours, and then acidified with dilute HCl to precipitate the crystals. The crystals were filtered, washed with water, and re-crystallized from dioxan to obtain N-phenoxyacetyl-4-nitro-L-phenylalanine as needles having melting point: 147° C. (2.4 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:13]=[C:12]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[N:20]=[CH:19][CH:18]=[N:17]4)[N:11]([CH:24]([C:26]3[CH:34]=[CH:33][C:29]([C:30](O)=[O:31])=[CH:28][CH:27]=3)[CH3:25])[N:10]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.Cl.[NH2:36][CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40].ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.CCOC(C)=O>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2[CH:13]=[C:12]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[N:20]=[CH:19][CH:18]=[N:17]4)[N:11]([CH:24]([C:26]3[CH:27]=[CH:28][C:29]([C:30]([NH:36][CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[O:31])=[CH:33][CH:34]=3)[CH3:25])[N:10]=2)[CH:3]=[C:2]([Cl:1])[CH:7]=1
Reactant: CC(c1ccc(C(=O)O)cc1)n1nc(-c2cc(Cl)cc(Cl)c2)cc1-c1ccc2nccnc2c1
Reactant: CCOC(=O)CCN
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCOC(=O)CCNC(=O)c1ccc(C(C)n2nc(-c3cc(Cl)cc(Cl)c3)cc2-c2ccc3nccnc3c2)cc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of the intermediate from step G (39.7 mg, 0.08 mmol) in 3 mL of anhydrous DMF was added ethyl β-alaninate hydrochloride (19 mg, 0.12), 1-hydroxy-7-azabenzo-triazole (17 mg, 0.12 mmol), N,N-diisopropylethyl amine (0.04 mL, 0.24 mmol), and 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (24 mg, 0.12 mmol). The reaction was left stirring at room temperature for 12 hours then diluted with EtOAc and washed with 1N HCl (2×), saturated sodium bicarbonate (2×), and brine (1×). The organic layer was then dried over anhydrous MgSO4, filtered and concentrated in vacuo. The resulting solid was purified by flash chromatography (30% EtOAc/Hexanes) to afford a light yellow solid. Enantiomers were then separated using SFC-HPLC semi-prep methodology with the conditions as follows: column=ChiralCel OJ 10×250 mm 10 micron, flow rate=10.0 mL/min, mobile Phase=40% MeOH (0.1% TFA)/CO2, column temperature=40° C., UV wavelength=248 nm, outlet pressure=100 bar, concentration=50 mg/mL in MeOH. Retention time: Isomer A=4.03 min; Isomer B=5.01 min. LC-MS: 4.20 min. (M+H)=589.48.
Reaction SMILES: [CH3:1][C:2](=O)[CH2:3][CH2:4][C:5](=O)[CH3:6].[NH2:9][C@@H:10]([CH3:13])[CH2:11][OH:12].C(OCC)(=O)C.CCCCCC>CO>[OH:12][CH2:11][C@@H:10]([N:9]1[C:2]([CH3:1])=[CH:3][CH:4]=[C:5]1[CH3:6])[CH3:13]
Reactant: C[C@H](N)CO
Reactant: CC(=O)CCC(C)=O
Solvent: CO
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: Cc1ccc(C)n1[C@@H](C)CO
Yield: 96.3 %

Procedure:
2,5-Hexanedione (3.6 mL, 30.7 mmol) was added to a solution of (S)-2-amino-1-propanol (2.44 g, 32.5 mmol) in 15 mL of methanol. The mixture was stirred at reflux for 2 h. After concentrating in vacuo, the residue was dissolved in 100 mL of ethyl acetate and washed with 50 1 mL of saturated aqueous sodium bicarbonate and 50 mL of saturated aqueous sodium chloride. The organic layer was dried (sodium sulfate), decanted, and evaporated to give a yellow solid. Flash column chromatography on 150 g of silica gel using 2.5 L of 15% ethyl acetate/hexane to furnish 4.53 g (96% yield) of (S)-1-(2-hydroxy-1-methylethyl)-2,5-dimethylpyrrole as a white solid.
Reaction SMILES: [C:1]1([CH:7]=[C:8]2[CH2:13][CH2:12][CH2:11][C:10](=[CH:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:9]2=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:22][CH2:23][CH2:24][NH:25][NH2:26]>CO>[C:1]1([CH:7]2[CH:8]3[C:9]([C:10](=[CH:14][C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[CH2:11][CH2:12][CH2:13]3)=[N:26][N:25]2[CH2:24][CH2:23][OH:22])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NNCCO
Reactant: O=C1C(=Cc2ccccc2)CCCC1=Cc1ccccc1
Solvent: CO
Product: OCCN1N=C2C(=Cc3ccccc3)CCCC2C1c1ccccc1

Procedure:
A suspension of the 2,6-bis(phenylmethylene)cyclohexanone from example 1a in methanol is treated with (2-hydroxyethyl)hydrazine. The mixture is heated and the resulting solution is refluxed for four hours, cooled, and the bulk of the methanol is evaporated. The resulting alcohol is triturated with ether, cooled overnight, filtered, and dried in vacuo.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:17](Br)=[CH:16][CH:15]=[C:14]2[C:10]=1[CH2:11][C:12](=[O:20])[N:13]2[CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:21]1[CH:26]=[CH:25][CH:24]=[C:23](B(O)O)[CH:22]=1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:8][C:9]1[C:17]([C:23]2[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=2)=[CH:16][CH:15]=[C:14]2[C:10]=1[CH2:11][C:12](=[O:20])[N:13]2[CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OB(O)c1cccnc1
Reactant: CN1C(=O)Cc2c1ccc(Br)c2OCc1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: COCCOC
Product: CN1C(=O)Cc2c1ccc(-c1cccnc1)c2OCc1ccccc1
Temperature: 130 °C

Procedure:
To 4-benzyloxy-5-bromo-1-methyl-1,3-dihydro-indol-2-one (100 mg, 0.301 mmol) was added 3-pyridineboronic acid (CAS#1692.25-7, 44.4 mg, 0.361 mmol), 1,2-dimethoxyethane (2 mL) and 2 M aqueous sodium carbonate (0.376 ml, 0.753 mmol). The reaction mixture was degassed and placed under an argon atmosphere, at which time resin bound tetrakis(triphenylphosphine)palladium(0), specifically polystyrene triphenylphosphine palladium (0) [PS—PPh3-Pd(0) (Biotage), 0.11 mmol/g loading, (82 mg, 0.0093 mmol)] was added. The reaction vessel was sealed and was heated by microwave irradiation at 130° C. for 2.5 hours. The reaction mixture was cooled to room temperature, diluted with dichloromethane and filtered through glass wool. The filtrate was further diluted with saturated aqueous sodium bicarbonate and the layers were separated. The aqueous layer was extracted two times with dichloromethane, and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0 to 100%) to afford 4-benzyloxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one; HRMS: (ESI) m/z 331.1447 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 3.16 (s, 3H), 3.77 (s 2H), 4.93 (s, 2H), 6.88 (d J=8.08 Hz, 1H), 7.16-7.21 (m, 2H), 7.27-7.31 (m, 3H), 7.35 (d, J=8.08 Hz, 1H), 7.41 (qd, 1H), 7.86 (dt, J=7.83, 2.02 Hz, 1H), 5.52 (dd, J=4.80, 1.77 Hz, 1H), 8.67 (dd, J=2.27, 0.76 Hz, 1H).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([N:12]2[CH:17]=[C:16]([Cl:18])[C:15](=[O:19])[C:14]([C:20]([O:22][CH3:23])=[O:21])=[C:13]2[CH3:24])[C:7]([CH3:11])=[CH:8][C:9]=1[CH3:10])([O-])=O>CN(C)C=O.[Ni]>[NH2:1][C:4]1[CH:5]=[C:6]([N:12]2[CH:17]=[C:16]([Cl:18])[C:15](=[O:19])[C:14]([C:20]([O:22][CH3:23])=[O:21])=[C:13]2[CH3:24])[C:7]([CH3:11])=[CH:8][C:9]=1[CH3:10]
Reactant: COC(=O)c1c(C)n(-c2cc([N+](=O)[O-])c(C)cc2C)cc(Cl)c1=O
Agent: [Ni]
Solvent: CN(C)C=O
Product: COC(=O)c1c(C)n(-c2cc(N)c(C)cc2C)cc(Cl)c1=O
Yield: 98 %

Procedure:
14.7 g (0.042 mol) 1-(3'-nitro-4',6'-dimethylphenyl)-5-chloro-3-methoxycarbonyl-2-methyl-4-pyridone are dissolved in 450 ml dimethylformamide and, after adding of 1.5 g Raney-Ni hydrogenated at normal pressure and 20°-25° C. The catalyst is filtered off and the filtrate is concentrated by evaporation of the solvent. Cristallisation of the residue from ethanol yields 13.2 g (98%) 1-(3'-amino-4',6'-dimethylphenyl)-5-chloro-3-methoxycarbonyl-2-methyl-4-pyridone, mp. 215° C.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][N:10]1[C:22]2[CH:21]=[CH:20][CH:19]=[C:18]([O:23][CH2:24][C:25]([O:27]C)=[O:26])[C:17]=2[C:16]2[C:11]1=[CH:12][CH:13]=[CH:14][C:15]=2[C:29](=[O:31])[NH2:30])#[N:2].[OH-].[Na+]>C(O)C>[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][N:10]1[C:22]2[CH:21]=[CH:20][CH:19]=[C:18]([O:23][CH2:24][C:25]([OH:27])=[O:26])[C:17]=2[C:16]2[C:11]1=[CH:12][CH:13]=[CH:14][C:15]=2[C:29](=[O:31])[NH2:30])#[N:2]
Reactant: COC(=O)COc1cccc2c1c1c(C(N)=O)cccc1n2Cc1ccccc1C#N
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: N#Cc1ccccc1Cn1c2cccc(OCC(=O)O)c2c2c(C(N)=O)cccc21
Yield: 100.7 %

Procedure:
A suspension of the {9-[(2-cyanophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl ester (110 mg, 0.266 mM) and 0.29 mL (0.29 mM) of 1 N NaOH in 5 mL of ethanol was sonicated for 2 hours at 25° C. The resultant white precipitate was collected by filtration, washed with small amounts of EtOH, diethyl ether, and hexanes, then dried in vacuo to afford 107 mg (95%) of the {9-[(2-cyanophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, sodium salt as a white powder. 1H NMR (DMSO-d6) δ7.9 (d, 1H, J=8 Hz), 7.6 (br s, 1H), 7.5 (d, 1H, J=8 Hz), 7.45-7.4 (m, 3H), 7.35 (t, 1H, J=8 Hz), 7.25 (t, 1H, J=8 Hz), 7.1 (d, 1H, J=8 Hz), 7.05 (d, 1H, J=8 Hz), 6.55 (d, 1H, J=8 Hz), 6.4 (d, 1H, J=8 Hz), 5.8 (s, 2H), and 4.3 (s, 2H). IR (KBr, cm−1) 2220, 1652, and 1613. MS (ES) m/e 398, 400.
Reaction SMILES: C(O[CH:4](OCC)[CH2:5][CH2:6][CH2:7][NH2:8])C.Cl.[Br:13][C:14]1[CH:15]=[C:16]([NH:21]N)[CH:17]=[CH:18][C:19]=1[F:20]>CO>[Br:13][C:14]1[CH:15]=[C:16]2[C:17]([C:5]([CH2:6][CH2:7][NH2:8])=[CH:4][NH:21]2)=[CH:18][C:19]=1[F:20]
Reactant: CCOC(CCCN)OCC
Reactant: NNc1ccc(F)c(Br)c1
Agent: Cl
Solvent: CO
Product: NCCc1c[nH]c2cc(Br)c(F)cc12
Temperature: 180 °C
Reaction time: 2.5 h
Yield: 116.7 %

Procedure:
4,4-Diethoxybutan-1-amine (4.72 g, 29.3 mmol) was added to (3-bromo-4-fluorophenyl)hydrazine hydrochloride (6.4 g, 27 mmol). The resulting mixture in an open round bottom flask was placed into a preheated oil bath at 180° C. The mixture was stirred at 180° C. for 2.5 h and then cooled to 120° C. Methanol (300 mL) was added, and the mixture was stirred at ambient temperature for 18 h. The resulting suspension was filtered through a silica gel plug, and the silica gel was then washed with methanol (5×300 mL). The combined methanol fractions were concentrated under vacuum to provide the crude title compound (8.1 g) as a yellow solid, which was used in the next step without further purification: ESI MS m/z 257 [M+H]+.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[O:9][CH2:10][C:11]1[CH:16]=[C:15]([CH3:17])[CH:14]=[CH:13][N:12]=1.CC1(C)C(C)(C)OB([C:26]2[CH:35]=[C:34]3[C:29]([CH2:30][CH2:31][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:33]3)=[CH:28][CH:27]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.O.Cl[Pd]Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].C(OCC)(=O)C>[F:8][C:6]1[CH:5]=[CH:4][C:3]([O:9][CH2:10][C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[CH:13][N:12]=2)=[C:2]([C:26]2[CH:35]=[C:34]3[C:29]([CH2:30][CH2:31][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:33]3)=[CH:28][CH:27]=2)[CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CCc2ccc(B3OC(C)(C)C(C)(C)O3)cc2C1
Reactant: Cc1ccnc(COc2ccc(F)cc2Br)c1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1ccnc(COc2ccc(F)cc2-c2ccc3c(c2)CN(C(=O)OC(C)(C)C)CC3)c1
Temperature: 120 °C

Procedure:
To a degassed mixture 2-{[(2-bromo-4-fluorophenyl)oxy]methyl}-4-methylpyridine (0.09 g), 1,1-dimethylethyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate (0.131 g) (for preparation see WO 2007/056710) and caesium carbonate (0.296 g) in dioxane:water (4:1, 5 ml) was added PdCl2.dppf (0.025 g). The reaction mixture was heated at 120° C. overnight. The reaction mixture was added to water and extraction was carried out with ethyl acetate. The organic layer was dried over sodium sulphate and the filtrate was concentrated in vacuo. The crude product was purified through silica, eluting with 0-12% ethyl acetate in hexane. Appropriate fractions were concentrated in vacuo to yield the title compound, 0.169 g, quantitative yield.
Reaction SMILES: N[C:2]1[CH:3]=[C:4]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:5]=[CH:6][C:7]=1[CH:8]([OH:14])[C:9]([O:11]CC)=[O:10].NC1C=CC(C2C=CC(C(O)C(OCC)=[O:36])=CC=2)=CC=1.OC1C=C(C2C=CC=CC=2)C=CC=1C(O)C(O)=O.OC1C=CC(C2C=CC(C(O)C(O)=O)=CC=2)=CC=1>>[OH:36][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[C:4]1[CH:5]=[CH:6][C:7]([CH:8]([OH:14])[C:9]([OH:11])=[O:10])=[CH:2][CH:3]=1
Reactant: CCOC(=O)C(O)c1ccc(-c2ccccc2)cc1N
Reactant: CCOC(=O)C(O)c1ccc(-c2ccc(N)cc2)cc1
Agent: O=C(O)C(O)c1ccc(-c2ccc(O)cc2)cc1
Agent: O=C(O)C(O)c1ccc(-c2ccccc2)cc1O
Product: O=C(O)C(O)c1ccc(-c2ccccc2O)cc1

Procedure:
When ethyl 3-amino-4-biphenylylglycolate or ethyl 4'-amino-4-biphenylylglycolate are used in the above procedure then the product prepared is 3-hydroxy-4-biphenylylglycolic acid or 4'-hydroxy-4-biphenylylglycolic acid.
Reaction SMILES: [CH2:1]([NH:3][C:4](=[O:20])[O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH:16]([CH3:19])[CH2:17][CH3:18])=[CH:11][CH:10]=1)[CH3:2].N1C=CC=CC=1.[C:27]1([S:33]Cl)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(Cl)Cl>[CH2:1]([N:3]([S:33][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:4](=[O:20])[O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][CH:16]([CH3:19])[CH2:17][CH3:18])=[CH:13][CH:14]=1)[CH3:2]
Reactant: CCNC(=O)OCCOc1ccc(OC(C)CC)cc1
Reactant: ClSc1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCC(C)Oc1ccc(OCCOC(=O)N(CC)Sc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To O-2-[4-(1-methylpropoxy)phenoxy]ethyl N-ethylcarbamate (1.50 g, 5.34 mmol) and pyridine (1 ml, 11.75 mmol) in 20 ml of methylene chloride at RT is added phenylsulfenyl chloride (1.54 g, 10.70 mmol). The reaction mixture is stirred for 2 hours, after which it is poured into ice water and extracted with ether. The combined organic layers are washed with 10% HCl, with water until neutral and with brine and dried. After filtration and removal of the solvent, the product is purified by prep. TLC to give O-2-[4-(1-methylpropoxy)phenoxy]ethyl N-ethyl-N-phenylsulfenylcarbamate, MS m/e 390 (M+ +H) (compound 23, Table A).
Reaction SMILES: CO.[OH-].[Na+].[CH:5]1([SH:11])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.O=O>[Co].C([O-])(=O)C.[Co+2].C([O-])(=O)C.O>[CH:5]1([S:11][S:11][CH:5]2[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]2)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: SC1CCCCC1
Agent: [Co+2]
Agent: [Co]
Agent: CC(=O)[O-]
Solvent: CO
Solvent: O
Product: C1CCC(SSC2CCCCC2)CC1
Temperature: 55 °C
Reaction time: 3 h
Yield: 83.8 %

Procedure:
This example is an inventive run illustrating the use of another soluble cobalt-containing catalyst system. The run also suggests that because of the enhanced catalyst activity of the cobalt-containing catalyst system, the reaction can be operated with less alcohol present. Into a 300 milliliter stainless steel reactor equipped as described in Example I was charged 12 grams of methyl alcohol, 2 grams of sodium hydroxide, 0.1 gram of cobalt acetate and 86 grams (0.74) moles of cyclohexyl mercaptan. The reactor was pressured to 240 psig with nitrogen, heated to 55° C. (131° F.) and then pressured to 300 psig with oxygen. The reaction was complete in 3 hours. The effluent was water washed and the oil layer dried on a Rotovap at 90°-100° C./20-40 Torr. (mm) to give a 100 percent selectivity and 83.8 percent yield of dicyclohexyl disulfide.
Reaction SMILES: CC(C)([O-])C.[K+].[Cl-].[CH3:8][O:9][CH2:10][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH2:30]([CH:37]1[CH2:42][C:41](=O)[CH2:40][CH2:39][N:38]1[C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C1COCC1>[CH2:30]([CH:37]1[CH2:42]/[C:41](=[CH:8]\[O:9][CH3:10])/[CH2:40][CH2:39][N:38]1[C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: COC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1Cc1ccccc1
Agent: CC(C)(C)[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: C1CCOC1
Product: CO/C=C1/CCN(C(=O)OC(C)(C)C)C(Cc2ccccc2)C1
Reaction time: 6 h
Yield: 34.1 %

Procedure:
Potassium tert-butoxide (4.49 mL, 1M in THF) was added over about 5 minutes to (methoxymethyl)triphenylphosphonium chloride (1.42 g, 4.15 mmol) suspended in anhydrous THF (25 mL) at 0° C. The resulting suspension was stirred at about this temperature for about 45 minutes at which time, tert-butyl 2-benzyl-4-oxopiperidine-1-carboxylate (1.0 g, 3.46 mmol) dissolved in THF (5 mL) was added. The reaction mixture was allowed to warm to ambient and stir for another 6 h. The reaction was quenched by the addition of ammonium chloride solution and then taken up in EtOAc. After washing twice with water and once with brine, the organic portion was dried over magnesium sulfate, filtered and concentrated. The resulting semi-solid residue was purified via silica gel chromatography to give (Z)-tert-butyl 2-benzyl-4-(methoxymethylene)piperidine-1-carboxylate (375 mg, 34%). LCMS (APCI+) m/z 218.1 [M+H]+; Rt=4.51 min.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][C:16]=1[N+:17]([O-])=O>C(O)C>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][C:16]=1[NH2:17]
Reactant: COC(=O)c1ccccc1Oc1cnccc1[N+](=O)[O-]
Solvent: CCO
Product: COC(=O)c1ccccc1Oc1cnccc1N

Procedure:
A solution of 2-(4-nitro-3-pyridinyloxy)benzoic acid methyl ester, N-oxide (30 g) in 1.5 L ethanol containing 1.5 g platinum oxide was hydrogenated for five hours at 50 psi. The mixture was filtered and concentrated to 26 g solid which was purified by flash chromatography (silica, 5% methanol in dichloromethane) to give 20 g of 2-(4-amino-3-pyridinyloxy)benzoic acid methyl ester and 4.5 g solid, d 200°. The latter material was purified by flash chromatography (silica, 10% methanol in dichloromethane) to give 3.4 g solid, d 200°. This material was recrystallized from ethanol/ether to give 2.5 g solid, d 200°.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.BrC1C=CC([N+]([O-])=[O:19])=CC=1.[OH-].[Cs+]>>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([OH:19])=[CH:3][CH:4]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1ccc(I)cc1
Reactant: O=[N+]([O-])c1ccc(Br)cc1
Agent: [Cs+]
Agent: [OH-]
Product: O=[N+]([O-])c1ccc(O)cc1

Procedure:
Following general operating mode A, 1-iodo-4-nitrobenzene or 1-bromo-4-nitrobenzene (249 mg or 202 mg, 1.0 mmol) were reacted at 110° C. with cesium hydroxide to obtain the expected product in the form of a yellow solid with respective yields of 90% and 82% (ethyl acetate/heptane 20:80).
Reaction SMILES: [C:1]([O:5][C:6](=[O:23])[NH:7][CH:8]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=1)[C:9](=[O:14])N(OC)C)([CH3:4])([CH3:3])[CH3:2].I[C:25]1[CH:30]=[CH:29][C:28]([O:31][C:32]([F:37])([F:36])[CH:33]([F:35])[F:34])=[CH:27][CH:26]=1>>[C:1]([O:5][C:6](=[O:23])[NH:7][CH:8]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=1)[C:9](=[O:14])[C:25]1[CH:26]=[CH:27][C:28]([O:31][C:32]([F:36])([F:37])[CH:33]([F:35])[F:34])=[CH:29][CH:30]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: FC(F)C(F)(F)Oc1ccc(I)cc1
Reactant: CON(C)C(=O)C(NC(=O)OC(C)(C)C)c1ccc(Cl)c(Cl)c1
Product: CC(C)(C)OC(=O)NC(C(=O)c1ccc(OC(F)(F)C(F)F)cc1)c1ccc(Cl)c(Cl)c1

Procedure:
The title compound was prepared from rac-[(3,4-dichloro-phenyl)-(methoxy-methyl-carbamoyl)-methyl]-carbamic acid tert-butyl ester (Intermediate 9) and 1-iodo-4-(1,1,2,2-tetrafluoro-ethoxy)benzene in analogy to Example 1a): MS (ISN): 494.1 and 496.2 (M−H.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][C:10](O)=[O:11].B.C1COCC1.Cl>C1COCC1>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][OH:11]
Reactant: O=C(O)Cc1ccc(F)cc1Br
Agent: B
Agent: Cl
Solvent: C1CCOC1
Product: OCCc1ccc(F)cc1Br
Temperature: 25 °C
Reaction time: 3 h
Yield: 92.5 %

Procedure:
To a solution of 2-(2-bromo-4-fluorophenyl)acetic acid (2.3 g, 9.87 mmol) in THF (20 mL) at 0° C. was added 1M BH3.THF comples (14.80 mL, 14.80 mmol) in THF and the resulting mixture was stirred at room temp for 3 h. 1N HCl (50 mL) was then added and the mixture was extracted with ethyl acetate (200 mL), washed with brine (50 mL), dried (Na2SO4), filtered and concentrated to afford 2-(2-bromo-4-fluorophenyl)ethanol (2.0 g, 9.13 mmol, 93% yield) as colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.33 (dd, J=8.4, 2.7 Hz, 1H), 7.30-7.24 (m, 1H), 7.01 (td, J=8.2, 2.6 Hz, 1H), 3.89 (q, J=6.6 Hz, 2H), 3.02 (t, J=6.6 Hz, 2H), 1.43 (t, J=5.8 Hz, 1H).