Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH:16][C:17]2[C:26]([NH:27][C:28]([NH:30][CH2:31][CH3:32])=S)=[CH:25][CH:24]=[CH:23][C:18]=2[C:19]([O:21][CH3:22])=[O:20])=[CH:11][CH:10]=1)#[N:2].NC1C(NCC2C=CC(C3C=CC=CC=3C#N)=CC=2)=C(C=CC=1)C(OC)=O>>[CH2:31]([NH:30][C:28]1[N:16]([CH2:15][C:12]2[CH:13]=[CH:14][C:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[C:1]#[N:2])=[CH:10][CH:11]=2)[C:17]2[C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:23][CH:24]=[CH:25][C:26]=2[N:27]=1)[CH3:32]
Reactant: CCNC(=S)Nc1cccc(C(=O)OC)c1NCc1ccc(-c2ccccc2C#N)cc1
Agent: COC(=O)c1cccc(N)c1NCc1ccc(-c2ccccc2C#N)cc1
Product: CCNc1nc2cccc(C(=O)OC)c2n1Cc1ccc(-c2ccccc2C#N)cc1

Procedure:
The title compound was prepared as colorless crystals (3.2 g, 32%) according to the procedure for Working Example 8 from methyl 2-[[(2'-cyanobiphenyl-4-yl)methyl]amino]-3-(3-ethylthioureido)benzoate (10.5 g), which was synthesized from methyl 3-amino-2-[[(2'-cyanobiphenyl-4-yl)methyl]amino]benzoate in substantially the same manner as Reference Example 5.
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:15])[N:9]2[CH2:12][CH:13]=O)=[CH:4][CH:3]=1.[NH:16]1[CH2:21][CH2:20][CH:19]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:18][CH2:17]1.C(Cl)(Cl)Cl.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CO>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:15])[N:9]2[CH2:12][CH2:13][N:16]2[CH2:17][CH2:18][CH:19]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:27])([CH3:26])[CH3:28])[CH2:20][CH2:21]2)=[CH:4][CH:3]=1
Reactant: O=CCn1c(=O)ccc2ccc(F)cc21
Reactant: CC(C)(C)OC(=O)NC1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CO
Product: CC(C)(C)OC(=O)NC1CCN(CCn2c(=O)ccc3ccc(F)cc32)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 117.3 %

Procedure:
A mixture of (7-fluoro-2-oxo-1(2H)-quinolinyl)acetaldehyde (594 mg; 2.89 mmol) and 1,1-dimethylethyl 4-piperidinylcarbamate (578 mg; 2.89 mmol) in a 1:1 mixture of chloroform and methanol (20 ml:20 ml) was stirred at rt under argon for 1 h. The mixture was then treated with NaBH(OAc)3 (1.83 g; 8.67 mmol) and stirred at rt for a 1 h. More 1,1-dimethylethyl 4-piperidinylcarbamate (297 mg; 1.45 mmol) was added and the reaction was stirred under the same conditions for a further 0.5 h. This was then again treated with NaBH(OAc)3 (915 mg; 4.34 mmol) and stirred at rt for a further 0.75 h. More 1,1-dimethylethyl 4-piperidinylcarbamate (118 mg; 0.578 mmol) was then added, the reaction was stirred at rt for a further 10 mins, followed by addition of NaBH(OAc)3 (366 mg; 1.73 mmol), the reaction was stirred for a further 25 mins. The solvents were removed and the crude residue purified by chromatography on silica gel using a 010% MeOH/DCM gradient to provide the impure desired compound (1.32 g, 117%)
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#C)=[C:7]([N+:13]([O-:15])=[O:14])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(#N)C.I(O)(=O)(=O)=[O:20].[OH2:24]>C(Cl)(Cl)(Cl)Cl.O.[Ru](Cl)(Cl)Cl>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([OH:20])=[O:24])=[C:7]([N+:13]([O-:15])=[O:14])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: O
Reactant: C#Cc1ccc(C(C)(C)C)cc1[N+](=O)[O-]
Reactant: [O-][I+3]([O-])([O-])O
Agent: Cl[Ru](Cl)Cl
Solvent: CC#N
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)(C)c1ccc(C(=O)O)c([N+](=O)[O-])c1
Reaction time: 1.5 h

Procedure:
4-tert-Butyl-1-ethynyl-2-nitro-benzene (1.662 g, 8.176 mmol) was dissolved in 20 mL carbon tetrachloride, 20 mL acetonitrile, and 40 mL water. Periodic acid (9.322 g, 40.89 mmol) was added followed by ruthenium(III)chloride hydrate (85 mg, 0.41 mmol). After stirring of 90 minutes, the resulting mixture was diluted with water and extracted with three portions of dichloromethane. The combined dichloromethane layers wee dried over anhydrous MgSO4, and concentrated in vacuo to yield 4-tert-Butyl-2-nitro-benzoic acid (1.924 g, 86.19 mmol).
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[CH3:9][O:10][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][C:18]=1[CH3:19])[C:14]#[N:15]>C(Cl)(Cl)(Cl)Cl.CCOCC.[W].C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[Br:1][CH2:19][C:18]1[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][C:11]=1[O:10][CH3:9]
Reactant: O=C1CCC(=O)N1Br
Reactant: COc1cc(C#N)ccc1C
Agent: [W]
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Solvent: CCOCC
Product: COc1cc(C#N)ccc1CBr
Yield: 65 %

Procedure:
N-Bromosuccinimide (3.2 g.) and benzoyl peroxide (0.005 g.) were added to a solution of 3-methoxy-4-methylbenzonitrile (2.65 g.) in dry carbon tetrachloride (90 ml.). The mixture was heated to reflux for 15 minutes using a 250 watt tungsten lamp. The cooled reaction mixture was diluted with petrolum ether (b.p. 60°-80° C., 90 ml.), insoluble material removed by filtration, and the filtrate evaporated. The solid residue was recrystallized from a mixture of dichloromethane and petroleum ether to give 4-bromomethyl-3-methoxybenzonitrile (W) (2.64 g. , 65% ) as a white solid, m.p. 87°-91° C.
Reaction SMILES: CCCCCC.[H-].[K+].[CH3:9][C:10]1[CH:14]=[CH:13][NH:12][N:11]=1.[CH3:15][O:16][C:17](=[O:26])[C:18]1[CH:23]=[CH:22][C:21](F)=[CH:20][C:19]=1[Cl:25]>CN(C)C=O>[CH3:15][O:16][C:17](=[O:26])[C:18]1[CH:23]=[CH:22][C:21]([N:12]2[CH:13]=[CH:14][C:10]([CH3:9])=[N:11]2)=[CH:20][C:19]=1[Cl:25]
Reactant: COC(=O)c1ccc(F)cc1Cl
Reactant: Cc1cc[nH]n1
Agent: [H-]
Agent: [K+]
Solvent: CCCCCC
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(-n2ccc(C)n2)cc1Cl
Temperature: 130 °C
Yield: 82.8 %

Procedure:
Under anhydrous conditions a stirred suspension of hexane washed potassium hydride (0.424 g, 10.6 mmol) in 5 mL of dimethylformamide was treated in one portion with 3-methyl pyrazole (0.85 mL, 10.6 mmol). After the gas evolution ceased, 2-chloro-4-fluorobenzoic acid methyl ester (2.0 g, 10.6 mmol) was added to the clear solution. The mixture was heated at 130° C. for 15 minutes, cooled, and partitioned between ethyl acetate and brine. The organic layer was washed with water and brine, and dried over sodium sulfate. Removal of solvent afforded 2.2 g of a yellow oil consisting of a mixture of 3-methyl and 5-methylpyrazole regioisomers. In addition, about 20% of the acid derived from hydrolysis of the ester was detected by analysis of the NMR spectrum of the crude product. The desired 3-methylpyrazole regioisomer was separated from the 5-methyl isomer of Example 16 by flash chromatography (on silica Merck-60, dichloromethane-hexane 2:1) and was isolated as a white solid (1.55 g).
Reaction SMILES: [CH:1](=[N:5]/[C@H:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH3:7])\[CH2:2][CH2:3][CH3:4].C[Si](C)(C)[O:16][C:17]([O:25][CH2:26][CH3:27])=[C:18]([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21]>CC1CCCO1>[CH2:23]([O:22][C:18]([O:19][CH2:20][CH3:21])([C@@H:1]([NH:5][C@H:6]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH3:7])[CH2:2][CH2:3][CH3:4])[C:17]([O:25][CH2:26][CH3:27])=[O:16])[CH3:24]
Reactant: CCC/C=N/[C@@H](C)c1ccccc1
Reactant: CCOC(OCC)=C(OCC)O[Si](C)(C)C
Solvent: CC1CCCO1
Product: CCC[C@H](N[C@@H](C)c1ccccc1)C(OCC)(OCC)C(=O)OCC
Temperature: 0 °C
Reaction time: 4 h
Yield: 119.2 %

Procedure:
With BF3OEt2: (S,E)-N-butylidene-1-phenylethanamine (Example 1, 10.0 g, 57.0 mmol) was dissolved in 250 mL 2-methyltetrahydrofuran and cooled to 0° C. BF3OEt2 (7.0 mL, 57.0 mmol) was added to the mixture followed by a solution of trimethyl((1,2,2-triethoxyvinyl)oxy)silane (Example 10, 11.34 g, 45.6 mmol) in 80 mL 2-methyltetrahydrofuran, and the mixture was stirred at 0° C. After four hours, further imine (1.8 g, 10.2 mmol) and BF3OEt2 (1.2 mL, 9.7 mmol) were added and the mixture was stirred at 0° C. for further three hours. The volume of the mixture was halved by evaporation, water was added, the mixture was neutralized (pH=7.2) with 2N NaOH, and the phases were separated. Removal of the solvent in vacuo yielded 19.1 g crude (S)-ethyl 2,2-diethoxy-3-(((S)-1-phenylethyl)amino)hexanoate as a 85.15 (syn:anti) diastereomeric mixture.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2C=CC(O)=CC=2)([CH3:10])[CH3:9])=[CH:4][CH:3]=1.[C-]#[N:19]>>[C:11]([C:8]([C:5]1[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=1)([CH3:9])[CH3:10])#[N:19]
Reactant: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Reactant: [C-]#N
Product: CC(C)(C#N)c1ccc(O)cc1

Procedure:
A preferred manner of practicing this invention constitutes heating a solventless mixture of Bisphenol A and cyanide ion in a closed vessel to about 185° C. and maintaining that temperature for about 20 hours to produce 4-(1-cyano-1-methylethyl)phenol. Preferred conversions and yields based on Bisphenol A are about 100 percent and 80 percent respectively.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[N:7][NH:8]2)([O-:3])=[O:2].[H-].[Na+].[CH3:15]I>CN(C=O)C>[CH3:15][N:8]1[C:9]2[C:5](=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=[CH:11][CH:10]=2)[CH:6]=[N:7]1
Reactant: O=[N+]([O-])c1cccc2[nH]ncc12
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cn1ncc2c([N+](=O)[O-])cccc21
Yield: 82 %

Procedure:
A solution of 4-nitroindazole (prepared according to the literature procedures Davies, R. R. J.C.S., 1955, 2412-2423; Porter, H. D. Org. Synth. Collect. Vol I, 20, 73-74.) (2.01 g, 12.3 mmol) was added slowly to a cold (ice/water), stirred suspension of NaH (440 mg, 18.4 mmol) in DMF (20 mL) under N2. The mixture was stirred for 30 min, and a solution of MeI (1.91 g, 13.5 mmol) in DMF (10 mL) was then added. Workup gave 1-methyl-4-nitroindazole (1.79 g, 82%); mp (EtOAc/petroleum ether) 138-139° C. Hydrogenation of this (6.70 g, 37.9 mmol) in absolute EtOH (300 mL) in the presence of Pd/C (1.00 g) gave 4-amino-1-methylindazole (4.23 g, 76%). A mixture of 4-amino-1-methylindazole (4.10 g, 27.9 mmol) and 2-bromo-3-nitrobenzoic acid (6.86 g, 27.9 mmol) were then reacted in a mixture of isopropanol/N-methylmorpholine in the presence of copper powder and CuI as above, giving 2-[(1-methyl-1H-indazol-4-yl)amino]-3-nitrobenzoic acid (439 mg, 5 %); mp (EtOAc/n-hexane) 257-260° C.; Reductive cyclisation of 2-[(1-methyl-1H-indazol-4-yl)amino]-3-nitrobenzoic acid with NaBH4 in 2 M NaOH as above gave 3-methyl-3H-pyrazolo[4,3-a]phenazine-10-carboxylic acid as a dark yellow solid (54%); mp (acetone) 320-323° C. [(CD3)2SO] δ 4.28 (s, 3 H, NCH3), 8.07 (t, J=7.9 Hz, 1 H, H-8), 8.10 (d, J=9.6 Hz 1H, H-4 or H-5), 8.39 (d, J=9.6 Hz 1H, H-4 or H-5), 8.52-8.60 (m, 2H, H-7 and H-9), 8.76 (s, 1 H, H-2), 14.90 (br s, 1 H, COOH).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[Br:8][C:9]1[C:18]([Br:19])=[C:17]([N+:20]([O-:22])=[O:21])[C:12]2[O:13][CH2:14][CH2:15][O:16][C:11]=2[C:10]=1[C:23](Cl)=[O:24]>CC(CC)C(=O)C>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:23]([C:10]2[C:11]3[O:16][CH2:15][CH2:14][O:13][C:12]=3[C:17]([N+:20]([O-:22])=[O:21])=[C:18]([Br:19])[C:9]=2[Br:8])=[O:24])[CH2:4][CH2:3]1
Reactant: O=C(Cl)c1c(Br)c(Br)c([N+](=O)[O-])c2c1OCCO2
Reactant: CN1CCNCC1
Agent: CCC(C)C(C)=O
Product: CN1CCN(C(=O)c2c(Br)c(Br)c([N+](=O)[O-])c3c2OCCO3)CC1
Temperature: 10 °C
Yield: 69.5 %

Procedure:
400 ml of methylethylacetone and 11 g of methylpiperazine were introduced into a balloon flask provided with an agitator and a thermometer. The mixture was cooled to 10° C. and then 41 g of 6,7-dibromo-8-nitro-1,4-benzodioxane-5-carbonyl chloride were added in portions with the temperature being maintained below 20° C. After agitation of the mixture, the crystals were dried off, washed with methylethylcetone and dried and then dissolved in water and reprecipitated by addition of 50 ml of 20% ammonia. The crystals were dried off, washed with water and dried. 33 g of 5-[(4-methyl-1-piperazinyl)-carbonyl]-6,7-dibromo-8-nitro-1,4-benzodioxane were obtained (M.P: 164° C.; yield: 69.6%).
Reaction SMILES: [C:1]1([NH:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.I[C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Cu].ClC1C=CC=CC=1Cl>[CH3:21][C:18]1[CH:19]=[CH:20][C:15]([N:7]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:16][CH:17]=1
Reactant: Cc1ccc(I)cc1
Reactant: c1ccc(Nc2ccccc2)cc1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Clc1ccccc1Cl
Product: Cc1ccc(N(c2ccccc2)c2ccccc2)cc1
Reaction time: 7 h
Yield: 81.4 %

Procedure:
To 30 ml of o-dichlorobenzene, 4.5 g (27 mmol) of diphenylamine, 11.0 g (51 mmol) of p-iodotoluene, 5.5 g (40 mmol) of anhydrous sodium carbonate and 1.1 g of copper powder were added. The mixture was heated and refluxed with stirring for 7 hours. After the reaction was completed, the reaction solution was filtered. The filtrate was successively washed with an aqueous 35% sodium thiosulfate solution and saturated brine. The organic layer was dried with anhydrous sodium sulfate, and thereafter the solvent was removed. The resulting crude reaction product was recrystallized from ethanol to obtain 4-methyltriphenylamine in an amount of 5.7 g (yield: 81.4%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO[CH:17](OC)[N:18]([CH3:20])[CH3:19]>>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11](=[O:14])[C:12](=[CH:17][N:18]([CH3:20])[CH3:19])[CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: COC(OC)N(C)C
Product: CN(C)C=C1CN(C(=O)OC(C)(C)C)CCC1=O
Reaction time: 6 h

Procedure:
A mixture of 1-tert-butoxycarbonyl piperidine-4-one and N,N-dimethylformamide dimethylacetal was stirred for 6 hours heated to reflux to give 1-tert-butoxycarbonyl-3-[(dimethylamino)methylene]piperidine-4-one. A mixture of the obtained 1-tert-butoxycarbonyl-3-[(dimethylamino)methylene]piperidine-4-one, 2-hydrazinoethanol and MeOH was stirred for two hours heated to reflux to give a mixture of 2-(5-tert-butoxycarbonyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-2-yl)ethanol and 2-(5-tert-butoxycarbonyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-yl)ethanol. A mixture of the obtained mixture, 4M HCl-EtOAc solution and EtOH was stirred for two hours at room temperature to give a mixture of 2-(4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-2-yl)ethanol dihydrochloride and 2-(4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-yl)ethanol dihydrochloride.
Reaction SMILES: [CH3:1][C:2]([CH2:4][CH:5]([C:12]1[C:21](=[O:22])[O:20][C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:13]=1[OH:23])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)=[O:3].C(=O)([O-])[O-].[Na+:28].[Na+].CC(C)=O.CC(=O)CC>O>[CH3:1][C:2]([CH2:4][CH:5]([C:12]1[C:21](=[O:22])[O:20][C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:13]=1[O-:23])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[Na+:28]
Reactant: CC(=O)CC(c1ccccc1)c1c(O)c2ccccc2oc1=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: CCC(C)=O
Solvent: O
Product: CC(=O)CC(c1ccccc1)c1c([O-])c2ccccc2oc1=O

Procedure:
Warfarin sodium is prepared by refluxing the pure warfarin acid with an excess of sodium carbonate in a polar solvent such as acetone or butanone, which may be either anhydrous or contain from about 1% to about 10% water. The unreacted sodium carbonate is preferably removed by filtration. The product is isolated by evaporating the solvent to dryness or by precipitating the salt by addition of a nonpolar solvent such as hexane, cyclohexane, heptane and the like, and filtering and drying the precipitate.
Reaction SMILES: CC([NH:8][C:9](=[O:12])[CH:10]=[CH2:11])(C)[CH2:3][C:4](=[O:6])[CH3:5].N>O>[C:9]([NH2:8])(=[O:12])[CH:10]=[CH2:11].[CH3:3][C:4]([CH3:5])=[O:6].[CH3:3][C:4]([CH3:5])=[O:6]
Reactant: C=CC(=O)NC(C)(C)CC(C)=O
Agent: N
Solvent: O
Product: C=CC(N)=O
Product: CC(C)=O

Procedure:
A process is disclosed for preparing N-(1,1-dimethyl-3-oxobutyl)acrylamide which comprises (1) contacting a dispersion of 5,6-dihydro-6-hydroxy-4,4,6-trimethyl-2-vinyl-1,3,3(4H)-oxazine-3-ium sulfate (1:1) in a water-immiscible organic solvent with a neutralizing or alkalizing amount of gaseous ammonia at a temperature between about 10° C. and 25° C. to form a solution of diacetone acrylamide in said organic solvent and a precipitate of crystalline ammonium sulfate; (2) separating the crystals of ammonium sulfate; (3) cooling the organic mother liquors recovered from step (2) to about -10° C. to 20° C. to crystallize N-(1,1-dimethyl-3-oxobutyl)acrylamide therefrom; and (4) recovering the crystals of N-(1,1-dimethyl-3-oxabutyl) acrylamide, washing the recovered crystals with a cold water-immiscible organic solvent and drying the same.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:16][CH2:15][CH:11]([C:12](O)=[O:13])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC)=O.[BH4-].[Na+]>O1CCCC1.CO>[C:1]([O:5][C:6]([N:8]1[CH2:16][CH2:15][CH:11]([CH2:12][OH:13])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)O)CC1
Agent: CCOC(=O)Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN1CCOCC1
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC(CO)CC1
Reaction time: 0.5 h
Yield: 92.4 %

Procedure:
A solution of 1-tert-butoxycarbonyl isonipecotic acid (40 g, 0.17 mol) and N-methylmorpholine (19 mL, 0.17 mol) in tetrahydrofuran (900 mL) at −10° C. was treated with ethyl chloroformate (17 mL, 0.17 mol). After 0.5 h, sodium borohydride was added (19.8 g, 0.5 mol) in one portion followed by slow addition of methanol. After gas evolution ceased, the mixture was concentrated and the residue was diluted with 10% aqueous acetic acid and partitioned between ethyl acetate and water. The aqueous layer was washed with EtOAc (2×) and the combined organic extracts were dried with magnesium sulfate, filtered, and concentrated to a solid residue which was purified by column chromatography (SiO2: 10 to 50% EtOAc:hexanes) providing the title compound (33.8 g, 90%) as a white solid.
Reaction SMILES: [CH2:1]([O:8][CH:9]1[CH2:14][CH2:13][C:12](=[O:15])[CH2:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:16](=[O:19])([O-])[O-].[NH4+:20].[NH4+:21].[C-]#N.[K+]>C(O)C>[NH:20]1[CH2:13][C:12](=[O:15])[NH:21][C:16]1=[O:19].[CH2:1]([O:8][CH:9]1[CH2:14][CH2:13][C:12](=[O:15])[CH2:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [NH4+]
Reactant: O=C([O-])[O-]
Agent: O=C1CCC(OCc2ccccc2)CC1
Agent: [C-]#N
Agent: [K+]
Solvent: CCO
Product: O=C1CNC(=O)N1
Temperature: 60 °C

Procedure:
4-Benzyloxycyclohexanone 41 is dissolved in 30 mL of 50% ethanol containing ammonium carbonate and potassium cyanide is added (Step 38). The mixture will be warmed to 60° C. for 2 h and evaporated to dryness in vacuo. The residue is extracted with 40 mL of hot methanol, filtered, and the filter cake washed with 20 mL of hot methanol. The methanol solutions are combined, solvent evaporated, and the residue chromatographed on silica gel using CH2Cl2 /methanol 90:10 to yield 42.
Reaction SMILES: [N+:1]1([O-])[C:2](=[CH:6][CH:7]=[C:8]([CH:12]=1)[C:9]([OH:11])=[O:10])C(O)=O.CC(OC(C)=O)=O.OC1C=CC(C(O)=O)=CN=1.C(Cl)[Cl:32]>CCN(CC)CC>[Cl:32][C:2]1[CH:6]=[CH:7][C:8]([C:9]([OH:11])=[O:10])=[CH:12][N:1]=1
Reactant: O=C(O)c1ccc(C(=O)O)[n+]([O-])c1
Reactant: ClCCl
Agent: O=C(O)c1ccc(O)nc1
Solvent: CCN(CC)CC
Solvent: CC(=O)OC(C)=O
Product: O=C(O)c1ccc(Cl)nc1
Yield: 40.8 %

Procedure:
A sludge of 50 g of CH2Cl2, 10 g of Et3N and 9.1 g of isocinchomeronic acid-N-oxide was placed in an autoclave. Under 4.5 atu. and at 65° C., a mixture of 10.2 g of Ac2O, 5 g of Et3N and 50 g of CH2Cl2 was additionally pumped in. At the end of the addition, the reaction mixture was processed as in Example 1. The yield was 40.8 percent of 2-chloro-5-pyridine carboxylic acid (6-chloronicotinic acid) and 44.2 percent of 2-hydroxy-5-pyridine carboxylic acid (6-hydroxynicotinic acid).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH2:7])[CH:2]=1.N1C=CC=CC=1.Cl[C:15]([O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:16]>CC#N>[C:18]1([O:17][C:15](=[O:16])[NH:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: Nc1cccnc1
Solvent: CC#N
Solvent: c1ccncc1
Product: O=C(Nc1cccnc1)Oc1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 80.1 %

Procedure:
To a solution consisting of pyridin-3-yl amine (9.49 g, 101 mmol) and pyridine (8.77 g, 111 mmol) in CH3CN (80 mL) at 0° C. was added phenyl chloroformate (15.8 g, 101 mmol) dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction was quenched with H2O (200 mL) and the resulting precipitate was filtered and dried under vacuum to provide the title compound as a tan solid (17.34 g, 80%). MS (ESI+): calcd for C12H10N2O2 m/z 214.07, found 215.3 (M+H)+. 1H NMR (500 MHz, d6-DMSO): 10.46 (s, 1H), 8.69 (d, J=2.4 Hz, 1H), 8.27 (dd, J=4.7, 1.4 Hz, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.47-7.41 (m, 2H), 7.37 (dd, J=8.4, 4.7 Hz, 1H), 7.31-7.22 (m, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH3:9][C:10]1([CH3:18])[CH2:16][C:15](=O)[O:14][C:12](=[O:13])[CH2:11]1.C.O.C(O)C>C(O)C>[OH:8][C:5]1[CH:6]=[CH:7][C:2]([N:1]2[C:12](=[O:13])[CH2:11][C:10]([CH3:18])([CH3:9])[CH2:16][C:15]2=[O:14])=[CH:3][CH:4]=1
Reactant: CC1(C)CC(=O)OC(=O)C1
Reactant: Nc1ccc(O)cc1
Solvent: O
Solvent: CCO
Product: CC1(C)CC(=O)N(c2ccc(O)cc2)C(=O)C1
Temperature: 165 °C
Yield: 50.2 %

Procedure:
A mixture of 4-aminophenol (3.27 g, 30.0 mmol) and 3,3-dimethylglutaric anhydride (4.26 g, 30.0 mmol) was heated in a round bottom flask at 165° C. for 1 h, followed by heating at 180° C. for 7 h. After cooling to room temperature the solid material was dissolved in hot ethanol, activated charcoal was added and the solution was heated at reflux for 1 h. The solid material was removed by hot filtration. The solvent was evaporated and the residue was crystallised from water/ethanol yielding the title compound (3.51 g, 50% yield, pink solid).
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([CH3:12])[C:3]=1[C:4]([O:6][CH3:7])=[O:5].[Br:13]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl.CCOCC>[Br:13][CH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([CH3:12])[C:3]=1[C:4]([O:6][CH3:7])=[O:5]
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)c1c(C)cccc1C
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: CCOCC
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1c(C)cccc1CBr
Reaction time: 0.33 h

Procedure:
To a solution of methyl 2,6-dimethyl-benzoate (22.0 g, 134 mmol, example 1) in CCl4 (250 mL) is added N-bromo-succinimide (19 g, 107 mmol) followed by benzoyl peroxide (1.0 g, 4.0 p mmol). The resulting solution is warmed to reflux and stirred at this temperature for 20 min. The reaction mixture is then allowed to cool before being diluted with ether (200 mL), filtered and concentrated. The residue is purified by flash chromatography (silica, 4% acetone in hexanes) to give the title compound. This product (approx. 85% purity, remainder is methyl 2,6dimethyl benzoate) is used without further purification. MS (EI) 242, 244 (M+, Br pattern).
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][CH:3]=1.[O:10]1[CH:14]=[CH:13][CH2:12][C:11]1=O>C1(C=CC(O)=CC=1)O>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:7]2[CH2:14][CH2:13][CH2:12][C:11]2=[O:10])=[CH:4][CH:3]=1
Reactant: O=C1CC=CO1
Reactant: NCc1ccc(F)cc1
Agent: Oc1ccc(O)cc1
Product: O=C1CCCN1Cc1ccc(F)cc1
Yield: 74.8 %

Procedure:
47 g (0.376 mol) of p-fluorobenzylamine, 30.4 g (0.353 mol) of furan-2-one and 0.4 g of hydroquinone are introduced into a 125 ml autoclave. After driving the air out of the apparatus by passing a stream of nitrogen through it, the mixture is heated to 250° for 6 hours. It is then cooled and distilled under reduced pressure. 51 g (yield=74.8%) of 1-p-fluorobenzyl-pyrrolidin-2-one are collected as a colourless liquid distilling at 103°-105° under a pressure of 0.01 mm of mercury and solidifying slowly. Melting point=37°-38°.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].O.[C:6]1([CH3:12])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>>[N+:1]([C:9]1[CH:10]=[CH:11][C:6]([CH3:12])=[CH:7][CH:8]=1)([O-:4])=[O:2]
Reactant: O=[N+]([O-])O
Reactant: Cc1ccccc1
Solvent: O
Product: Cc1ccc([N+](=O)[O-])cc1

Procedure:
reacting toluene with nitric acid having an acid concentration of between about 60 and about 75 percent by weight, based upon the total amount of acid plus water, at a reaction temperature of between about 60° C. and about 75° C., and employing between about 3 and about 5 moles of nitric acid per mole of toluene, to produce mononitrotoluene,