Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:16][OH:17])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].CO[C:20]([CH3:22])=[CH2:21]>CC(C)=O.B(F)(F)F.CCOCC>[CH3:15][O:14][C:12](=[O:13])[CH2:11][CH2:10][C@H:9]1[CH2:16][O:17][C:20]([CH3:22])([CH3:21])[N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7]
Reactant: COC(=O)CC[C@@H](CO)NC(=O)OC(C)(C)C
Reactant: C=C(C)OC
Agent: FB(F)F
Solvent: CCOCC
Solvent: CC(C)=O
Product: COC(=O)CC[C@H]1COC(C)(C)N1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 89.9 %

Procedure:
(S)-Methyl 4-(tert-butoxycarbonylamino)-5-hydroxypentanoate (24 g, 97.2 mmol) and isopropenyl methyl ether (88.8 g, 854.6 mmol) was dissolved in acetone (2000 mL) and BF3.Et2O (0.82 mL, 5.84 mmol) was added at rt. The mixture was stirred for 1 hr at rt. The reaction was quenched by addition of Et3N (11.6 mL). The reaction solution was washed with aqueous saturated NaHCO3 (200 mL) and evaporated, and (S)-tert-butyl 4-(3-methoxy-3-oxopropyl)-2,2-dimethyloxazolidine-3-carboxylate (25.1 g, 90%) was obtained as an oil, which was used in the next step without further purification.
Reaction SMILES: [C:1]([CH2:3][C:4]1([N:15]2[CH:19]=[C:18]([C:20]3[C:21]4[CH:28]=[CH:27][N:26]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[C:22]=4[N:23]=[CH:24][N:25]=3)[CH:17]=[N:16]2)[CH2:7][N:6](C(OC(C)(C)C)=O)[CH2:5]1)#[N:2].[ClH:37]>C1COCC1.O1CCOCC1>[ClH:37].[ClH:37].[CH3:35][Si:33]([CH3:34])([CH3:36])[CH2:32][CH2:31][O:30][CH2:29][N:26]1[C:22]2[N:23]=[CH:24][N:25]=[C:20]([C:18]3[CH:17]=[N:16][N:15]([C:4]4([CH2:3][C:1]#[N:2])[CH2:5][NH:6][CH2:7]4)[CH:19]=3)[C:21]=2[CH:28]=[CH:27]1
Reactant: CC(C)(C)OC(=O)N1CC(CC#N)(n2cc(-c3ncnc4c3ccn4COCC[Si](C)(C)C)cn2)C1
Agent: Cl
Solvent: C1COCCO1
Solvent: C1CCOC1
Product: C[Si](C)(C)CCOCn1ccc2c(-c3cnn(C4(CC#N)CNC4)c3)ncnc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 99 %

Procedure:
To a solution of tert-butyl 3-(cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylate (2 g, 3.9 mmol) in 10 mL of THF was added 10 mL of 4 N HCl in dioxane. The solution was stirred at room temperature for 1 hour and concentrated in vacuo to provide 1.9 g (99%) of the title compound as a white powder solid, which was used for the next reaction without purification. LC-MS: [M+H]+=410.3.
Reaction SMILES: [I:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].C(Cl)(=O)C([Cl:14])=O>CN(C=O)C.C(Cl)Cl>[I:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([Cl:14])=[O:5]
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)c1ccccc1I
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(Cl)c1ccccc1I

Procedure:
2-Iodobenzoic acid (65.92 g, 0.266 mol), oxalyl chloride (40.5 g, 0.319 mol), CH2Cl2 (200 mL) and DMF (10 drops) were stirred at RT overnight. The reaction solution was concentrated, toluene was added and the solution concentrated to afford the crude 2-iodobenzoyl chloride.
Reaction SMILES: [N+:1]([C:4]1[CH:24]=[CH:23][C:7]([C:8]([N:10]2[C:16]3[CH:17]=[CH:18][S:19][C:15]=3[CH2:14][N:13]3[CH:20]=[CH:21][CH:22]=[C:12]3[CH2:11]2)=[O:9])=[CH:6][CH:5]=1)([O-])=O.C(OCC)(=O)C>C(O)C.[Pd]>[NH2:1][C:4]1[CH:24]=[CH:23][C:7]([C:8]([N:10]2[C:16]3[CH:17]=[CH:18][S:19][C:15]=3[CH2:14][N:13]3[CH:20]=[CH:21][CH:22]=[C:12]3[CH2:11]2)=[O:9])=[CH:6][CH:5]=1
Reactant: O=C(c1ccc([N+](=O)[O-])cc1)N1Cc2cccn2Cc2sccc21
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: Nc1ccc(C(=O)N2Cc3cccn3Cc3sccc32)cc1
Reaction time: 5 h

Procedure:
A mixture of 5 mmol of 4,10-dihydro-4-(4-nitrobenzoyl)-5H-pyrrolo-[1,2-a]thieno[3,2-e][1,4]diazepine in 25 ml of ethyl alcohol and 25 ml of ethyl acetate containing 0.2 g of 10% Pd/C is hydrogenated for 5 hours. The reaction mixture is filtered through a pad of diatomaceous earth. The filtrate is concentrated in vacuo to a solid which is purified by flash chromatography on silica gel to give the desired product.
Reaction SMILES: [OH-].[K+].C([O:5][C:6](=[O:14])[CH:7]=[C:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)C>O.CO>[C:8]1(=[CH:7][C:6]([OH:14])=[O:5])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1
Reactant: CCOC(=O)C=C1CCCCC1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)C=C1CCCCC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 97.6 %

Procedure:
A mixture of KOH (1.0 g, 18 mmol) dissolved in water (25 mL) and Intermediate 3 (1.6 g, 9.5 mmol) dissolved in MeOH (5 mL) was stirred for 18 hours at room temperature. The reaction was refluxed for one hour, cooled, then extracted with EtOAc. The aqueous layer was acidified with 1N NCl and extracted with EtOAc, washed with brine, dried (Na2SO4), and concentrated in vacuo to provide 1.3 g (100%) of Intermediate 4. 1H NMR (DMSO-d6) δ: 1.55 (br s, 6H) 2.1 (m, 2H), 2.8 (m, 2H), 5.5 (s, 1H), 11.9 (s, 1H); MS ES−m/e 139.1 (p−1).
Reaction SMILES: Br[C:2]1[C:10]2[O:9][C:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[N:7][C:6]=2[CH:5]=[C:4]([O:19][CH3:20])[CH:3]=1.[Cu][C:22]#[N:23].C(N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=O>CN(C)C=O>[CH3:20][O:19][C:4]1[CH:3]=[C:2]([C:22]#[N:23])[C:10]2[O:9][C:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[N:7][C:6]=2[CH:5]=1
Reactant: COc1ccc(-c2nc3cc(OC)cc(Br)c3o2)cc1
Reactant: N#C[Cu]
Agent: O=C(O)CN(CCN(CC(=O)O)CC(=O)O)CC(=O)O
Solvent: CN(C)C=O
Product: COc1ccc(-c2nc3cc(OC)cc(C#N)c3o2)cc1
Yield: 97.5 %

Procedure:
A solution of 7-bromo-5-methoxy-2-(4-methoxyphenyl)-1,3-benzoxazole (200 mg, 0.60 mmol), in anhydrous N,N dimethylformamide (135 mL) was stirred and heated to reflux under dry nitrogen with copper(I) cyanide (80 mg, 0.90 mmol) for 4 h. The mixture was cooled and poured into an excess of aqueous ethylenediaminetetraacetic acid. Isolation of the crude product gave the nitrile (164 mg, 98% yield) as tan needles from (30% EtOAc/petroleum ether); m.p. 180–183° C.; MS m/e 281 (M+H)+.
Reaction SMILES: [CH2:1]([C:3]1[CH:7]=[CH:6][S:5][CH:4]=1)[CH3:2].C([Li])CCC.CCCCCC.CN(C)[CH:21]=[O:22].[Cl-].[NH4+]>C(OCC)C>[CH2:1]([C:3]1[CH:7]=[C:6]([CH:21]=[O:22])[S:5][CH:4]=1)[CH3:2]
Reactant: CN(C)C=O
Reactant: CCc1ccsc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCOCC
Solvent: CCCCCC
Product: CCc1csc(C=O)c1
Temperature: 60 °C
Reaction time: 2 h

Procedure:
3-Ethylthiophene (2 g, 17.8 mmol) dissolved in diethyl ether (18 ml) was added with a solution of n-butyl lithium in hexane (1.5 M, 14 ml, 21.4 mmol) at room temperature and refluxed by heating at 60° C. for 15 minutes. The reaction solution was returned to room temperature and added dropwise with dimethylformamide (2 ml, 23.2 mmol) dissolved in diethyl ether. After the reaction solution was stirred for 2 hours at room temperature, the reaction was stopped with saturated aqueous ammonium chloride, and the reaction solution was extracted with chloroform. The collected organic layer was washed with saturated brine, then dried over magnesium sulfate and concentrated under reduced pressure.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](Br)[N:3]=1.[CH3:9][S-:10].[Na+]>CN(C=O)C.C(OCC)C>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([S:10][CH3:9])[N:3]=1
Reactant: Brc1cccc(Br)n1
Reactant: C[S-]
Agent: [Na+]
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CSc1cccc(Br)n1

Procedure:
To a solution of 2,6-dibromopyridine (0.50 g, 2.11 mmol) in DMF (21 mL) was added sodium thiomethoxide (0.16 g, 2.32 mmol) and the solution was allowed to react overnight. The solution was then diluted with ethyl ether, washed with water, dried over magnesium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography to yield the title compound. 1H NMR (600 MHz, CDCl3): 7.32 (t, J=7.3 Hz, 1H), 7.15 (dd, J=9.6, 1.2 Hz, 1H), 7.12 (dd, J=9.0, 0.6 Hz, 1H), 2.55 (s, 1H).
Reaction SMILES: Cl.[N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[CH2:12]Cl.[OH:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=1)[CH2:18][OH:19].C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[CH2:12][O:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=1)[CH2:18][OH:19]
Reactant: OCc1cccc(O)c1
Reactant: ClCc1ccc2ccccc2n1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: OCc1cccc(OCc2ccc3ccccc3n2)c1
Temperature: 70 °C

Procedure:
A mixture of 12.8 g (0.06 mol) of 2-quinolinylmethyl chloride HCl, 7.5 g (0.06 mol) of 3-hydroxybenzyl alcohol, and 18 g of potassium carbonate in 50 ml of DMF is heated at 70° C. overnight. The reaction mixture is poured into water, and the precipitated product is collected, filtered and dried to give 3-(2-quinolinylmethyloxy)benzyl alcohol.
Reaction SMILES: [C:1]([O:7]CC)(=O)[CH2:2][C:3]([CH3:5])=O.C(O)(=O)C.[CH3:14][C:15]1[CH:16]=[C:17]([NH2:20])[NH:18][N:19]=1>COC(C)(C)C>[CH3:14][C:15]1[CH:16]=[C:17]2[NH:20][C:3]([CH3:5])=[CH:2][C:1](=[O:7])[N:18]2[N:19]=1
Reactant: Cc1cc(N)[nH]n1
Reactant: CCOC(=O)CC(C)=O
Solvent: CC(=O)O
Solvent: COC(C)(C)C
Product: Cc1cc2[nH]c(C)cc(=O)n2n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 101.9 %

Procedure:
Add ethyl acetoacetate (128 g, 0.98 mol) dropwise to an acetic acid solution (500 mL) of 5-methyl-2H-pyrazol-3-ylamine (100 g, 0.95 mol), keeping the temperature at 25-28° C. Heat the mixture at reflux for 10 h and then cool to room temperature. Add the reaction to tert-butyl methyl ether (5 L) cooled to 5° C., keeping the temperature below 10° C. Stir for 1 h at 5° C., and filter. Dry the resulting material in vacuo overnight to provide a white solid (158 g, 96%).
Reaction SMILES: [CH3:1][O:2][C:3]([CH2:5][CH2:6][CH:7]1[C:15]2[C:10](=[C:11]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])[C:12]([CH3:17])=[CH:13][C:14]=2[CH3:16])[NH:9][CH2:8]1)=[O:4].I[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33].C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>CN(C=O)C>[CH2:26]([N:9]1[C:10]2[C:15](=[C:14]([CH3:16])[CH:13]=[C:12]([CH3:17])[C:11]=2[NH:18][C:19](=[O:24])[C:20]([CH3:21])([CH3:23])[CH3:22])[CH:7]([CH2:6][CH2:5][C:3]([O:2][CH3:1])=[O:4])[CH2:8]1)[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]
Reactant: CCCCCCCCI
Reactant: COC(=O)CCC1CNc2c(NC(=O)C(C)(C)C)c(C)cc(C)c21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCCCCCCCN1CC(CCC(=O)OC)c2c(C)cc(C)c(NC(=O)C(C)(C)C)c21
Temperature: 40 °C
Reaction time: 10 h
Yield: 82.2 %

Procedure:
N-[3-(2-Methoxycarbonylethyl)-4,6-dimethylindolin-7-yl]-2,2-dimethylpropanamide (1.0 g) was dissolved in DMF (10 ml) and 1-iodooctane (1.44 g) and K2CO3 (830 mg) were added, which was followed by stirring at 40° C. for 10 hr. AcOEt (100 ml) was added, and after washing with water, the mixture was dried over anhydrous sodium sulfate. AcOEt was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: benzene/AcOEt=20/1-5/1) to give 1.1 g of the title compound.
Reaction SMILES: [CH:1]1[C:14]2[C:13](=O)[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[S:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[OH-].[K+].O.NN.O>C(O)CO>[CH:1]1[C:14]2[CH2:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[S:6][C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: O=c1c2ccccc2sc2ccccc12
Agent: NN
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: OCCO
Product: c1ccc2c(c1)Cc1ccccc1S2
Temperature: 140 °C
Reaction time: 2 h
Yield: 61.2 %

Procedure:
Thioxanthone (0.21 g) was dissolved in ethylene glycol (1.5 ml). Potassium hydroxide (0.19 g) and hydrazine monohydrate (0.15 ml) were added to the solution. The mixture was heated at 140° C. with stirring for 2 hr and then at 200° C. for 4 hr. The temperature of the reaction solution was returned to room temperature. Water was then added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous MgSO4. The solvent was then removed by distillation under the reduced pressure. The residue was purified by column chromatography on silica gel (chloroform) to give thioxanthene (0.12 g).
Reaction SMILES: [C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:10](N(CC)CC)C.COC(ON=C(C#N)C(OCC)=O)=O>CO>[C:1]([O:9][CH3:10])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCN(CC)CC
Reactant: O=C(O)c1ccccc1
Agent: CCOC(=O)C(C#N)=NOC(=O)OC
Solvent: CO
Product: COC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Benzoic acid (1.22 g) and triethylamine (1.4 ml) are dissolved in methanol (15 ml), and ethyl 2-methoxycarbonyloxyimino-2-cyanoacetate (2.0 g) is added thereto. The resulting mixture is stirred at room temperature for 2 hours and then extracted with ethyl acetate. The extract is treated as in Example A to give methyl benzoate (0.9 g) as an oil.
Reaction SMILES: [NH2:1][CH2:2][C:3]([OH:5])=[O:4].[CH:6]([P:8](=[O:11])([OH:10])[OH:9])=O>>[CH2:2]([NH:1][CH2:6][P:8]([OH:11])([OH:10])=[O:9])[C:3]([OH:5])=[O:4]
Reactant: NCC(=O)O
Reactant: O=CP(=O)(O)O
Product: O=C(O)CNCP(=O)(O)O
Yield: 27 %

Procedure:
Reaction of glycine and formylphosphonic acid was carried out under the conditions described in Example 6 except that the initial pH was 4.0. A 27% yield of glyphosate was obtained.
Reaction SMILES: N1C=CN=C1.[Si:6](Cl)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[NH2:14][C:15]1[CH:16]=[C:17]([OH:21])[CH:18]=[CH:19][CH:20]=1.[Cl-].[Na+]>CN(C)C=O>[Si:6]([O:21][C:17]1[CH:16]=[C:15]([NH2:14])[CH:20]=[CH:19][CH:18]=1)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]
Reactant: Nc1cccc(O)c1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: [Cl-]
Agent: [Na+]
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)Oc1cccc(N)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 68 %

Procedure:
6.81 g (100 mmol) of imidazole and 9.04 g (60 mmol) of tert-butyl-dimethylsilyl chloride are added to a solution of 5.46 g (50 mmol) of 3-aminophenol in 13.5 ml of N,N-dimethylformamide. The resulting reaction mixture is stirred at room temperature for 12 h. After addition of a saturated aqueous sodium chloride solution, the mixture is extracted with ethyl acetate. The organic phase is dried over sodium sulphate. The crude product obtained after removal of the solvent by distillation is purified by flash chromatography. 7.62 g (34 mmol, 68%) of the desired product are obtained.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[CH3:5][C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][N+:7]=1[O-:13].[OH-].[Na+]>S(=O)(=O)(O)O>[CH3:5][C:6]1[CH:11]=[C:10]([N+:1]([O-:4])=[O:2])[C:9]([CH3:12])=[CH:8][N+:7]=1[O-:13]
Reactant: Cc1ccc(C)[n+]([O-])c1
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: Cc1c[n+]([O-])c(C)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
260 ml of fuming nitric acid (d =1.5) were added dropwise to 840 ml of concentrated sulphur-ic acid while cooling. 348,2 g of 2,5-dimethy1pyridine 1-oxide were subsequently added portionwise at 0-5° . The mixture was stirred at room temperature for 1 hour, then heated to 90° within 3 hours, left at this temperature overnight and, after cooling, poured on to 6 kg of ice. The mixture was adjusted to pH 3 with concentrated sodium hydroxide solution and extracted three times with 2 1 of methylene chloride. The combined organic phases were washed with 4 1 of water, dried over sodium sulfate and evaporated in vacuo. The residue was crystallized from methylene chloride/petroleum ether and there was obtained 2,5-dimethyl-4-nitropyridine 1-oxide of melting point 142-144° .
Reaction SMILES: [C:1](Cl)(=O)[C:2]([Cl:4])=[O:3].[Cl:7][C:8]1[N:16]=[C:15]([Cl:17])C=C[C:9]=1[C:10](O)=O.CN(C)C=O>C(Cl)Cl>[Cl:17][C:15]1[N:16]=[C:8]([Cl:7])[CH:9]=[CH:10][C:1]=1[C:2]([Cl:4])=[O:3]
Reactant: O=C(O)c1ccc(Cl)nc1Cl
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)c1ccc(Cl)nc1Cl
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Oxalyl chloride (2M solution, 20 mL) (Aldrich, Milwaukee, Wis.) was added to a mixture of 2,6-dichloronicotinic acid (6.2 g) and N,N-dimethylformamide (DMF) (0.5 mL) in DCM (100 mL) at room temperature. After stirring at room temperature for 2 hours, the reaction was concentrated to give 2,6-dichloro-nicotinoyl chloride (used directly in the next step).
Reaction SMILES: C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[CH3:20][O:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26]Cl)=[CH:24][CH:23]=1.[Cl:30][SiH:31]([Cl:33])[Cl:32]>>[CH3:20][O:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26][Si:31]([Cl:33])([Cl:32])[Cl:30])=[CH:24][CH:23]=1
Reactant: COc1ccc(CCl)cc1
Reactant: Cl[SiH](Cl)Cl
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Product: COc1ccc(C[Si](Cl)(Cl)Cl)cc1
Yield: 45 %

Procedure:
In the same apparatus and procedure as Example 1 above, 0.056 g (0.2 mmol) of tricyclohexylphosphine, 0.271 ml (2.0 mmol) of 4-methoxybenzyl chloride, and 1.00 ml (9.91 mmol) of trichlorosilane were reacted at 150° C. for 2 hrs. The resulting mixture was distilled to give 0.23 g of (4-methoxybenzyl)trichlorosilane (yield; 47%).
Reaction SMILES: N1CCNCC1.[N:7]1([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[O:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31]Cl)=[CH:27][CH:26]=1>>[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[O:24][C:25]1[CH:26]=[CH:27][C:28]([CH2:31][N:10]2[CH2:11][CH2:12][N:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:8][CH2:9]2)=[CH:29][CH:30]=1
Reactant: CCOC(=O)N1CCNCC1
Reactant: ClCc1ccc(Oc2ccccn2)cc1
Agent: C1CNCCN1
Product: CCOC(=O)N1CCN(Cc2ccc(Oc3ccccn3)cc2)CC1

Procedure:
As depicted in Scheme 5, the known piperazine intermediate, for example, ethyl 1-piperazinecarboxylate (2000-2001 Aldrich Chemical catalog, pg 795), was reacted with the known methyl halide, for example 4-(2-pyridyloxy)phenylmethyl chloride (WO 97/26252) under basic conditions in an appropriate solvent, affording the corresponding ethyl ester, ethyl 4-[(4-(2-pyridyloxy)phenyl)methyl]piperazinecarboxylate (AA). Intermediate (AA) was then oxidized with, for example 30% hydrogen peroxide, providing the corresponding 4-oxide, ethyl 4-[(4-(2-pyridyloxy)phenyl)methyl]-4-oxypiperazinecarboxylate (BB), which in turn was decarboxylated with a strong aqueous base, providing the corresponding free piperazine 4-oxide, for example 2-[4-(4-oxypiperazin-1-ylmethyl)phenoxy]pyridine (CC).
Reaction SMILES: [NH2:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][OH:4].[OH-].[Na+].[CH:10](=O)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[BH4-].[Na+]>C(OCC)C>[CH2:10]([NH:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][OH:4])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=Cc1ccccc1
Reactant: N[C@@H](CO)C(=O)O
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Product: O=C(O)[C@H](CO)NCc1ccccc1
Temperature: 5 °C
Yield: 39.3 %

Procedure:
A 5 L 3-neck round bottom flask was charged with L-serine (313 g, 3.0 mol) and 2N sodium hydroxide solution (1.5 L). Stirring was begun and benzaldehyde (322.4 g, 3.0 mol) added. After 15 minutes at room temperature the solution was cooled to 5° C. and sodium borohydride (35.0 g, 0.93 mol) was added in small portions so as to maintain the temperature below 10° C. Once the addition was complete the solution was allowed to warm to room temperature and stir for 2 h. At this point, a second portion of benzaldehyde (322.4 g, 3.0 mol) was added and the solution stirred for 15 minutes. The solution was cooled to 5° C. and sodium borohydride (35.0 g, 0.93 mol) added, again maintaining the temperature below 10° C. The reaction mixture was then warmed to room temperature and stirred for 2 h. Diethyl ether (1 L) was added, the solution stirred 5–10 minutes and the ether layer separated. The pH of the aqueous layer was then adjusted to 6 with 37% hydrochloric acid. Filtration of the resulting solids and recrystallization of the wet cake from water afforded 230 g (40%) of (S)-(+)-N-benzylserine after drying at 45° C. overnight.
Reaction SMILES: N[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5](O)=[CH:4][C:3]=1Cl.CN1CCN(C)C1=O.C(=O)([O-])[O-].[K+].[K+].C(N(CCCC)C1C=C(O)C=CC=1)CCC>O>[CH:9]1[C:8]2[C:7](=[O:17])[C:6]3[C:15](=[CH:2][CH:3]=[CH:4][CH:5]=3)[C:14](=[O:16])[C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: Nc1c(Cl)cc(O)c2c1C(=O)c1ccccc1C2=O
Agent: CCCCN(CCCC)c1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCN(C)C1=O
Solvent: O
Product: O=C1c2ccccc2C(=O)c2ccccc21
Temperature: 140 °C
Reaction time: 3 h

Procedure:
One part by weight of 1-amino-2-chloro-4-hydroxyanthraquinone, 10 parts by weight of 1,3-dimethyl-2-imidazolidinone, 1.0 part by weight of potassium carbonate and 1.0 part by weight of N,N-di-n-butyl-m-aminophenol were mixed at room temperature, and then heated to 140° C. While this temperature was maintained, the reaction was conducted for 3 hours. The reaction mixture was then cooled to room temperature, charged into 90 parts by weight of water, and extracted with toluene. After the solution was separated, toluene was distilled off under reduced pressure, and the residue was purified through silica gel column chromatography to obtain an anthraquinone compound as coloring matter No. 9 (yield 90%) in Table 1.
Reaction SMILES: [CH2:1](Br)[CH:2]=[CH2:3].C1(S([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH2:24][C:25]4[CH:34]=[CH:33][C:32]5[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=5)[N:26]=4)[CH:21]=3)[C:16]([CH2:35][C:36]3[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=3)=[C:15]2[CH2:43][C:44]([CH3:50])([CH3:49])[C:45]([O:47]C)=[O:46])(=O)=O)C=CC=CC=1.[Na]>>[CH2:1]([N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH2:24][C:25]3[CH:34]=[CH:33][C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[N:26]=3)[CH:21]=2)[C:16]([CH2:35][C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=2)=[C:15]1[CH2:43][C:44]([CH3:50])([CH3:49])[C:45]([OH:47])=[O:46])[CH:2]=[CH2:3]
Reactant: COC(=O)C(C)(C)Cc1c(Cc2ccc(Cl)cc2)c2ccc(OCc3ccc4ccccc4n3)cc2n1S(=O)(=O)c1ccccc1
Reactant: C=CCBr
Agent: [Na]
Product: C=CCn1c(CC(C)(C)C(=O)O)c(Cc2ccc(Cl)cc2)c2ccc(OCc3ccc4ccccc4n3)cc21

Procedure:
The title compound was prepared under the conditions described in Step A and Step B of Example 38, but substituting allyl bromide for the benzenesulfonyl chloride from Example 38 (Step A). Anal. C, H, N for sodium salt·2 H2O Calc. C 66.38; H 5.74; N 4.69 Found C 66.57; H 5.75; N 4.73.
Reaction SMILES: N#N.[Br:3][C:4]1[CH:5]=[C:6]([C:10](=[O:12])[CH3:11])[CH:7]=[CH:8][CH:9]=1.COC(OC)OC.[CH2:20](O)[CH2:21][OH:22]>>[Br:3][C:4]1[CH:5]=[C:6]([C:10]2([CH3:11])[O:22][CH2:21][CH2:20][O:12]2)[CH:7]=[CH:8][CH:9]=1
Reactant: CC(=O)c1cccc(Br)c1
Reactant: OCCO
Agent: N#N
Solvent: COC(OC)OC
Product: CC1(c2cccc(Br)c2)OCCO1
Temperature: 95 °C

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 3′-bromoacetophenone (4.67 mL, 33.89 mmol) in ethylene glycol (36.4 mL) was treated with trimethylorthoformate (7.58 mL, 69.14 mmol) followed by LiBF4 (648 mg, 6.78 mmol). The reaction mixture was heated at 95° C. for 3.5 h. The reaction mixture was cooled to rt and partitioned between ether (100 mL) and sat. aq. Na2CO3 (25 mL). The layers were separated and the aq. layer extracted twice with ether (50 mL). The combined org. extracts were dried over Na2SO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue by FC (9:1 hept-EA) gave the title compound as a dark yellow oil. TLC: rf (9:1 hept-EA)=0.44. LC-MS-conditions 02: tR=1.00 min.