Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[Cl:10].[N:11]([O-:13])=[O:12].[Na+]>Cl.O.[Cu-]=O>[N+:11]([C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[Cl:10])([O-:13])=[O:12]
Reactant: N#Cc1ccc(N)c(Cl)c1
Reactant: O=N[O-]
Agent: O=[Cu-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: N#Cc1ccc([N+](=O)[O-])c(Cl)c1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
To an ice cold solution of 4-amino-3-chlorobenzonitrile (1 g, 6.6 mmol) in concentrated HCl (2.5 mL) plus water (2.5 mL) a chilled solution of sodium nitrite (0.74 g, 1.62 eq) in water (3.6 mL) is added dropwise to maintain the reaction temperature <0° C. After stirring at 0° C. for 10 min, the mixture is added portion-wise to an ice cold solution of sodium nitrite (3.29 g, 7.22 eq) and copper(I) oxide (349 mg, 0.37 eq) in water 14.5 mL). Stirring is continued at 0° C. for 40 min, and then at room temperature for 0.5 h. The reaction mixture is extracted with dichloromethane (2×), the combined organic layers washed with saturated aqueous sodium chloride, dried (MgSO4), concentrated, and purified by silica gel chromatography to give 4-nitro-3-chlorobenzonitrile. 1H NMR (CDCl3): δ 7.96 (d, J=8.24 Hz, 1 h), 7.88 (d, J=1.65 Hz, 1H), 7.63 (dd, J=1.65, 8.24 Hz, 1H.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7](O)=[O:8].O=S(Cl)[Cl:15]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([Cl:15])=[O:8]
Reactant: O=S(Cl)Cl
Reactant: COc1ccc(Cl)cc1C(=O)O
Product: COc1ccc(Cl)cc1C(=O)Cl
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of the 5-chloro-2-methoxybenzoic acid (0.94 g, 5.0 mmol) and SOCl2 (10 mL) was warmed to reflux and was allowed to stir for 2 h. The mixture was cooled to ambient temperature, concentrated under reduced pressure and diluted with 10 mL toluene. This material was again concentrated under reduced pressure and was again diluted with 10 mL toluene. This concentration and dilution was repeated for an addition time and the crude material was carried on without further purification or characterization.
Reaction SMILES: C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.CCCCCC[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32].CO[C:35]1[CH:36]=[C:37]2[C:42](=[CH:43][CH:44]=1)[CH2:41][CH2:40][CH2:39][CH2:38]2.O(C(C)C)C(C)C.C1(C)C(C2C(C)=CC=CC=2)=CC=CC=1.CC1C=C(O)C=CC=1>CC(OC)(C)C>[CH3:32][C:31]1[CH:26]=[CH:27][C:28]([C:35]2[CH:36]=[C:37]3[C:42](=[CH:43][CH:44]=2)[CH2:41][CH2:40][CH2:39][CH2:38]3)=[CH:29][CH:30]=1
Reactant: CCCCCCCCCCCCC
Reactant: COc1ccc2c(c1)CCCC2
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Agent: Cc1ccccc1-c1ccccc1C
Solvent: CC(C)OC(C)C
Solvent: Cc1cccc(O)c1
Solvent: COC(C)(C)C
Product: Cc1ccc(-c2ccc3c(c2)CCCC3)cc1
Temperature: 25 °C
Yield: 75 %

Procedure:
In a reaction flask was placed NiCl2(PCy3)2 (49.0 mg, 0.0710 mmol), PCy3 (44.0 mg, 0.157 mmol), tridecane (333 mg, 1.806 mmol, as an internal standard), and 6-methoxy-1,2,3,4-tetrahydronaphthalene (222 mg, 1.368 mmol). The solvent in the Grignard reagent (1 M in ether, 3.70 mmol) was exchanged with i-Pr2O (8.0 mL) and MTBE (2.0 mL) and this solution added to the above catalyst mixture under a nitrogen atmosphere at room temperature. The resulting solution was stirred for several minutes at room temperature and then warmed to 80° C. for 15 hours. A sample was withdrawn and quenched with an aqueous sodium citrate solution (1 M). The resulting aqueous solution was extracted with ethyl acetate. GC analysis of the organic phase showed the presence of 6-(4-methylphenyl)-1,2,3,4-tetrahydronaphthalene (1.030 mmol, 75% yield) and 6-methoxy-1,2,3,4-tetrahydronaphthalene (0.131 mmol) and bitoluene (0.376 mmol) and m-methylphenol (0.220 mmol) in the reaction mixture.
Reaction SMILES: [C:1]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)(=[O:5])[CH:2](C)[CH3:3]>O>[C:1]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)(=[O:5])[CH2:2][CH3:3]
Reactant: CC(C)C(=O)c1ccccc1
Solvent: O
Product: CCC(=O)c1ccccc1
Reaction time: 5.5 h
Yield: 2191.5 %

Procedure:
Example 1 was repeated except that no water was present in the feed mixture fed to the reactor; the feed rate was 279 ml/hr, the reaction time was 5.5 hours. Analysis of the condensed organic layer by gas chromatography indicated that 5.04 pounds of isobutyrophenone were produced per 100 pounds of propiophenone.
Reaction SMILES: [Cl:1][CH2:2][C:3]1[C:8]([C:9]([O:11][CH3:12])=[O:10])=[CH:7][CH:6]=[CH:5][N:4]=1.C1C=C(Cl)C=C(C(OO)=[O:21])C=1>C(Cl)Cl>[Cl:1][CH2:2][C:3]1[C:8]([C:9]([O:11][CH3:12])=[O:10])=[CH:7][CH:6]=[CH:5][N+:4]=1[O-:21]
Reactant: COC(=O)c1cccnc1CCl
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: COC(=O)c1ccc[n+]([O-])c1CCl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Methyl 2-(chloromethyl)pyridine-3-carboxylate (4.45 g, 23.98 mmol) was taken up in DCM (50 mL) and mCPBA (5.91 g, 26.4 mmol) was added. The resulting solution was stirred at room temperature overnight. The reaction mixture was then purified directly by silica gel chromatography (0-20% MeOH/EtOAe) to give methyl 2-(chloromethyl)pyridine-3-carboxylate 1-oxide as a white solid.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[C:9]([OH:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[CH3:12]O>S(=O)(=O)(O)O>[CH3:1][C:2]1[CH:10]=[C:9]([OH:11])[CH:8]=[CH:7][C:3]=1[C:4]([O:6][CH3:12])=[O:5]
Reactant: Cc1cc(O)ccc1C(=O)O
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1ccc(O)cc1C

Procedure:
2-Methyl-4-hydroxybenzoic acid was heated in methanol under the influence of sulfuric acid catalyst to convert it into its methyl ester. One mole of the methyl 2-methyl-4-hydroxybenzoate thus obtained was reacted with two moles of hydrogen in the presence of 5% palladium-carbon catalyst. This reaction was carried out in isopropyl alcohol at a temperature of 150°-170° C. and a hydrogen pressure of 20-40 kg/cm2. After the reaction mixture was filtered to recover the catalyst therefom, the filtrate was distilled to obtain 3-methylcyclohexanone-4-carboxylic acid methyl ester as the distillate at 112°-120° C./5 mmHg.
Reaction SMILES: Cl[CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C:3]1=O.[NH2:9][C:10]([NH2:12])=[S:11]>O1CCCC1>[S:11]1[C:3]2[CH2:4][CH2:5][CH2:6][CH2:7][C:2]=2[N:9]=[C:10]1[NH2:12]
Reactant: O=C1CCCCC1Cl
Reactant: NC(N)=S
Solvent: C1CCOC1
Product: Nc1nc2c(s1)CCCC2
Yield: 73 %

Procedure:
A stirred mixture of 2-chlorocyclohexanone (200 mg, 1.5 mmol) and thiourea (114 mg, 1.5 mmol) in tetrahydrofuran (20 ml) was heated at reflux for 6 hours. The solution was concentrated under reduced pressure and the amine was purified by flash column chromatography using ethylacetate/hexane 1/1 as eluent to afford a colourless oil (169 mg, 74%).
Reaction SMILES: [CH2:1]([NH2:4])[CH:2]=[CH2:3].C(O[SiH](OCC)OCC)C.N[CH2:16][CH2:17][CH2:18][Si:19]([O:26][CH2:27][CH3:28])([O:23][CH2:24][CH3:25])[O:20][CH2:21][CH3:22]>[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Rh].[Rh].[Rh].[Rh].C1(C)C=CC=CC=1>[CH2:1]([NH2:4])[CH:2]=[CH2:3].[NH2:4][CH:17]([CH3:16])[CH2:18][Si:19]([O:26][CH2:27][CH3:28])([O:23][CH2:24][CH3:25])[O:20][CH2:21][CH3:22]
Reactant: CCO[Si](CCCN)(OCC)OCC
Agent: [Rh]
Agent: CCO[SiH](OCC)OCC
Agent: [C-]#[O+]
Solvent: C=CCN
Solvent: Cc1ccccc1
Product: CCO[Si](CC(C)N)(OCC)OCC
Temperature: 110 °C

Procedure:
A three-neck flask equipped with a reflux condenser, stirring rod and thermometer was charged with 14 grams of allylamine (0.25 mole), 41 grams of triethoxy silane (0.25 mole) and 30 ml. of toluene, and heated in an oil bath maintained at a temperature of 110° C. When the temperature of the mixture reached 85° C., 0.22 gram of tetrarhodium dodecacarbonyl was added to the mixture as a catalyst. About 30 minutes after the addition of the catalyst, the reaction temperature reached 110° C. At the end of the period the reaction mixture was subjected to gas chromatography analysis. It was found that gamma-aminopropyl triethoxy silane was obtained in a yield of 68% on an allylamine basis, while the yield of beta-aminopropyl triethoxy silane was 4.9% on an allylamine basis.
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:9])[CH2:4][CH2:5][CH2:6][CH2:7][OH:8].[CH2:10](Br)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.O>CN(C=O)C>[CH2:10]([O:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][OH:9])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: BrCc1ccccc1
Reactant: OCCCCCO
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: OCCCCCOCc1ccccc1
Temperature: -20 °C
Reaction time: 0.5 h

Procedure:
31.5 g of sodium hydride (60%) is introduced at room temperature in portions in 900 ml of absolute DMF. 104.8 ml of 1,5-pentanediol in 450 ml of absolute DMF is added in drops to the suspension that is cooled to −20° C. in such a way that the internal temperature does not exceed −15° C. After the addition has been completed, a solution of 121 ml of benzyl bromide in 870 ml of absolute DMF is quickly added in drops, and then the reaction mixture is stirred for 30 minutes at room temperature. The reaction is completed by careful addition of 315 ml of water. For working-up, the reaction mixture is stirred into 1.5 l of water and extracted 3 times with 1 l of ether in each case. The ethereal phases are combined, washed with water, dried on magnesium sulfate and concentrated by evaporation in a vacuum. Chromatography on silica gel with a hexane-ethyl acetate gradient yields 85 g of 5-benzyloxy-pentan-1-ol as an oil.
Reaction SMILES: [P:1]([OH:4])([OH:3])[OH:2].Cl.[NH2:6][CH2:7][CH2:8][CH:9]([CH2:11][NH2:12])[OH:10].C=O>>[PH:1](=[O:2])([OH:4])[OH:3].[NH2:6][CH2:7][CH2:8][CH:9]([CH2:11][NH2:12])[OH:10]
Reactant: OP(O)O
Agent: C=O
Agent: Cl
Agent: NCCC(O)CN
Product: O=[PH](O)O
Reaction time: 2 h

Procedure:
To a 500 ml three neck flask fitted with a reflux condenser and dropping funnel is added 131.2 grams (1.12 moles) 70% phosphorous acid and 207.2 grams (2.1 moles) 37% hydrochloric acid. Aminoethyl ethanolamine, 42.1 grams (0.40 mole) is then added dropwise while stirring. The mixture is then heated to reflux and 97.3 grams (1.2 moles) 37% aqueous formaldehyde is added dropwise during 1 hour. Reflux is continued for 2 hours after completion of the formaldehyde addition. The mixture is then cooled and bottled.
Reaction SMILES: CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[N:23]1[C:28]2[NH:29][C:30]3[CH:38]=[CH:37][N:36]=[CH:35][C:31]=3[CH2:32][CH:33]([OH:34])[C:27]=2[CH:26]=[CH:25][CH:24]=1.S(=O)(O)[O-].[Na+]>ClCCl.O.C(=O)(O)[O-].[Na+]>[N:23]1[C:28]2[NH:29][C:30]3[CH:38]=[CH:37][N:36]=[CH:35][C:31]=3[CH2:32][C:33](=[O:34])[C:27]=2[CH:26]=[CH:25][CH:24]=1
Reactant: OC1Cc2cnccc2Nc2ncccc21
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=C([O-])O
Agent: O=S([O-])O
Solvent: ClCCl
Solvent: O
Product: O=C1Cc2cnccc2Nc2ncccc21
Reaction time: 1 h
Yield: 89.8 %

Procedure:
Dess-Martin periodinane (0.810 g, 1.91 mmol) was added to a solution of 6,11-dihydro-5H-dipyrido[2,3-b:3′,4′-f]azepin-5-ol (0.370 g, 1.74 mmol, Intermediate D-5) in dichloromethane (30 mL) under an atmosphere of nitrogen and stirred for 1 h. The yellow mixture was poured into a solution of sodium bisulfite in water and stirred for 5 minutes. The mixture was then diluted with dichloromethane and sodium bicarbonate was added to adjust the pH to 8-9. The mixture was extracted three times with dichloromethane and the combined extracts were dried over sodium sulfate, filtered, and concentrated. The crude product residue was adsorbed onto silica gel and chromatographed on a silica gel column eluting with 10% methanol/dichloromethane to provide the desired product as a light tan solid (330 mg, 90%). 1H NMR (DMSO-d6): δ 10.55 (s, 1H), 8.51 (dd, 1H), 8.42 (s, 1H), 8.35 (d, 1H), 8.18 (dd, 1H), 7.33 (d, 1H), 7.06 (dd, 1H), 3.82 (s, 2H). LC/MS: 212 (M+H)+.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][N:10]([C:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=3)[CH2:9][CH2:8]2)=[CH:3][CH:2]=1.[H-].[Na+].[CH2:22]([O:24][C:25](=[O:31])[CH2:26][CH:27]([CH3:30])[CH2:28]Br)[CH3:23]>CN(C=O)C>[CH3:28][CH:27]([CH2:30][O:19][C:16]1[CH:17]=[CH:18][C:13]([N:10]2[CH2:9][CH2:8][N:7]([C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)[CH2:12][CH2:11]2)=[CH:14][CH:15]=1)[CH2:26][C:25]([O:24][CH2:22][CH3:23])=[O:31]
Reactant: Oc1ccc(N2CCN(c3ccncc3)CC2)cc1
Reactant: CCOC(=O)CC(C)CBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)CC(C)COc1ccc(N2CCN(c3ccncc3)CC2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred suspension of 4-[4-(4-pyridyl)piperazin-1-yl]phenol (1.02 g) in dry DMF (10 ml) was added sodium hydride (60% dispersion in mineral oil, 0.16 g) and the mixture stirred for 1 hour at room temperature. To the resulting solution was added ethyl-4-bromo-3-methylbutyrate and the mixture stirred for 16 hours. Solvent was evaporated and the residue partitioned between water and dichloromethane. Insoluble material was removed by centrifugation. The organic layer was filtered through phase separating paper (Whatman IPS) and the residue was purified by flash chromatography on silica gel by elution with methanol/dichloromethane/concentrated ammonia (50/950/5) to give ethyl 3-methyl-4-[4-[4-(4-pyridyl)piperazin-1-yl]phenoxy]butyrate (0.27 g) which was hydrolysed in methanol (3 ml) and aqueous sodium hydroxide (1N, 2 ml) for 2 hours at room temperature. The solution was evaporated and the residue purified by reverse phase h.p.l.c (water/acetonitrile/0.1% TFA gradient) to give a glass which crystallised on trituration with ether to give the title compound (0.08 g): m.p. 169°-171° C.; NMR(d6DMSO) δ 13.45(1H,broad), 2.07(1H,broad) 8.27(2H,d), 7.28(2H,d), 6.9(4H,m), 3.80(6H,m), 3.16(4H,t), 2.45(1H,m), 2.37(1H,m), 2.12(1H,m), 1.0(3H,d); m/e 356(M+H)+ ; calculated for C22 H25N3O4F3. 0.5 H2O: C, 55.2; H, 5.6; N, 8.9. Found: C, 55.3; H, 5.6; N, 8.7%.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:8]1[CH2:13][CH2:12][CH:11]=[CH:10][CH:9]=1>C1COCC1>[CH:2]1([NH:1][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:7][CH2:6][CH2:5][CH:4]=[CH:3]1
Reactant: C1=CCCC=C1
Reactant: Nc1ccccc1
Solvent: C1CCOC1
Product: C1=CC(Nc2ccccc2)CCC1
Reaction time: 0.02 h
Yield: 86.8 %

Procedure:
Twelve enantioselective Examples are shown in Table 5 below (entries 1-12). A typical procedure is as follows: [Pd(π-allyl)Cl]2 (2.3 mg, 0.0063 mmol) and the (R,R)-Naphthyl-Trost ligand (10.9 mg, 0.0138 mmol) were dissolved in 0.1 mL of dry THF in a screw-capped vial. After stirring for one min, aniline (11.4 μL, 0.125 mmol) was added, and the color of the solution turned bright yellow. After addition of cyclohexadiene (47.6 μL, 0.500 mmol), the vial was sealed with a cap that contained a PTFE septum, and the reaction mixture was stirred at room temperature for 120 h. After removal of all volatile compounds using a rotary evaporator, the residue was purified by chromatography on silica gel (Hexanes : EtOAc=200:1) to give 18.8 mg (87%) of N-cyclohex-2-en-1-ylaniline as a colorless oil with 89% ee and the [α]D24° C. value of −84.5 (c 1.0222, CH2Cl2)
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:20][CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:21][CH3:22])[CH:17]=3)[C:12]2=O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C1(C)C=CC=CC=1.P(Br)(Br)[Br:32]>C1COCC1>[Br:32][C:12]1[C:13]2[C:18](=[CH:17][C:16]([O:21][CH3:22])=[CH:15][CH:14]=2)[CH2:19][CH2:20][C:11]=1[C:8]1[CH:9]=[CH:10][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:6][CH:7]=1
Reactant: BrP(Br)Br
Reactant: COc1ccc2c(c1)CCC(c1ccc(S(C)(=O)=O)cc1)C2=O
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: COc1ccc2c(c1)CCC(c1ccc(S(C)(=O)=O)cc1)=C2Br
Temperature: 110 °C
Reaction time: 0.5 h

Procedure:
Combine 2-(4-methanesulfonylphenyl)-6-methoxytetralone (1.0 eq.), hyflo (20%/weight), and toluene (7.5 volumes). Add PBr3 (1.5˜1.75 eq.) in one portion while stirring at room temperature. Heat contents to reflux (˜110° C.) overnight. Upon reaction completion, as judged by HPLC analysis (usually 15 hours), cool solution to 45° C. and slowly add 20 volumes THF. Stir for 30 minutes at 45° and filter warm over a pad of hyflo. The pad is washed with 2×2 volumes THF at 45° C. Concentrate filtrate to approximately 7 volumes. Add 7.5 volumes water to the remaining mixture keeping the temperature below 40° C. (NOTE: initial addition of water is very exothermic with large evolution of HBr). Cool slurry to room temperature and stir for 2 to 3 hours. Filter over a polypropylene pad and wash with 2×2 volumes water. Dry filter cake overnight at 60° C. under vacuum to give 1-bromo-2-(4-methanesulfonylphenyl)-3,4-dihydro-6-methoxynaphthalene.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:12][C:13](=[O:21])[CH2:14][C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[C:6]([CH:11]=1)[C:7]([O:9]C)=O.CO[Na]>O1CCCC1.CO>[Br:1][C:2]1[CH:11]=[C:6]2[C:5](=[CH:4][CH:3]=1)[NH:12][C:13](=[O:21])[CH:14]([C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1)[C:7]2=[O:9]
Reactant: COC(=O)c1cc(Br)ccc1NC(=O)Cc1cccnc1
Agent: CO[Na]
Solvent: CO
Solvent: C1CCOC1
Product: O=C1Nc2ccc(Br)cc2C(=O)C1c1cccnc1
Temperature: 20 °C
Reaction time: 8 h

Procedure:
Into a 100-mL round-bottom flask was placed a solution of methyl 5-bromo-2-[2-(pyridin-3-yl)acetamido]benzoate (3 g, 7.73 mmol, 1.00 equivalent, purity 90%, Intermediate 51, step a) in tetrahydrofuran (30 mL). A 2.38 M solution of MeONa in MeOH (freshly prepared by dissolving 2.74 g of Na in 50 mL of anhydrous MeOH solution, 11.7 mL, 27.85 mmol, 4.00 equivalents) was then added. The resulting solution was stirred overnight at 20° C., and the precipitate was collected by filtration to give the title compound as a white solid.
Reaction SMILES: [CH2:1]([O:4][C:5](OCCC)=[N:6][NH:7][C:8]([O:10]C)=O)[CH2:2][CH3:3].[CH3:16][NH2:17]>CO>[CH2:1]([O:4][C:5]1[N:17]([CH3:16])[C:8](=[O:10])[NH:7][N:6]=1)[CH2:2][CH3:3]
Reactant: CCCOC(=NNC(=O)OC)OCCC
Reactant: CN
Solvent: CO
Product: CCCOc1n[nH]c(=O)n1C
Reaction time: 3 h
Yield: 93.1 %

Procedure:
In an autoclave, 10.02 g (44.3 mmol) of methyl N′-dipropoxymethylenehydrazinecarboxylate, 3.94 g of 39% strength solution of methylamine (49.9 mmol) in methanol and 46 g of methanol were initially charged. After 3 hours at 150° C., the solvent was distilled off. The crude substance was taken up in water (20 ml) and extracted repeatedly with methylene chloride. The organic solution was concentrated, giving 6.48 g of 5-propoxy-4-methyl-2,4-dihydro-1,2,4-triazol-3-one with a content of 50%, which corresponds to a yield of 46%.
Reaction SMILES: C([O:24][CH:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[Br:33])[CH3:26])(=O)CCCCCCCCCCCCCCCCCCCCC>O>[Br:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[C@@H:25]([OH:24])[CH3:26]
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)OC(C)c1ccccc1Br
Solvent: O
Product: C[C@H](O)c1ccccc1Br
Yield: 82 %

Procedure:
Interesterification was carried out by using 3 g of Lipase QL, 50 g of (R,S)-1-(2-bromophenyl)ethanol, and 150 g of tribehen under the same conditions as in Example 3 at 105° C. for a period of 20 hours. The water content of the reaction system was 0.01% by weight, and 90% of the lipase particles had a particle size of 30 to 50 μm. Gas chromatography of the reaction mixture revealed that 45 mol % of (R,S)-1-(2-bromophenyl)ethanol had been converted to 1-(2-bromophenyl)ethyl behenate. The reaction mixture was treated in the same manner as in Example 3 and subjected to simple distillation at 110° C. and 5 mmHg to give (S)-(-)-1-(2-bromophenyl)ethanol (yield: 82%; chemical purity: 99.9%; optical purity: 81.5% ee). On the other hand, the residue, i.e., (R)-(+)-1-(2-bromophenyl)ethanol behenic acid ester was acid-hydrolyzed in the same manner as in Example 2 to obtain (R)-(+)-1-(2-bromophenyl)ethanol (yield: 75.6%; chemical purity: 99.8%; optical purity: 99.0% ee).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:16]=[N:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=2)[CH2:3][CH2:2]1.[C:17]1([C:23]2[C:24]([C:32]3[CH:39]=[CH:38][C:35]([CH:36]=O)=[CH:34][CH:33]=3)=[N:25][C:26]3[N:27]([CH:29]=[CH:30][N:31]=3)[CH:28]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>CN1C(=O)CCC1.C(O)(=O)C.C(N(CC)CC)C>[C:17]1([C:23]2[C:24]([C:32]3[CH:33]=[CH:34][C:35]([CH2:36][N:1]4[CH2:2][CH2:3][CH:4]([C:7]5[CH:16]=[N:15][C:14]6[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=6)[N:8]=5)[CH2:5][CH2:6]4)=[CH:38][CH:39]=3)=[N:25][C:26]3[N:27]([CH:29]=[CH:30][N:31]=3)[CH:28]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: c1ccc2nc(C3CCNCC3)cnc2c1
Reactant: O=Cc1ccc(-c2nc3nccn3cc2-c2ccccc2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CN1CCCC1=O
Solvent: CCN(CC)CC
Product: c1ccc(-c2cn3ccnc3nc2-c2ccc(CN3CCC(c4cnc5ccccc5n4)CC3)cc2)cc1
Reaction time: 1 h

Procedure:
195 mg (0.6 mmol) 2-Piperidine-4-ylquinoxaline are dissolved in 4.9 mL NMP. After addition of 0.19 mL triethylamine the reaction mixture is stirred for one hour. 170 mg (0.57 mmol) 4-(6-Phenyl-imidazo[1,2-a]pyrimidin-7-yl)-benzaldehyde (intermediate example 1.0) and 0.06 mL acetic acid are added. The reaction mixture is stirred overnight at room temperature. 132 mg (0.63 mmol) NaBH(OAc)3, are added in portions and the reaction mixture is stirred at room temperature for 18 hours. Additionally 75 mg NaBH(OAc)3 and 0.03 mL acetic acid are added and the stirring is continued for 23 hours. The reaction mixture is treated with saturated NaHCO3 and stirred vigorously for one hour. The precipitate is filtered off, washed with water and dried. After chromatography of the precipitate on silica gel (dichloromethane/methanol) 127.4 mg (45.2%) of the pure product are obtained. Another 66.1 mg (23.4%) of slightly contaminated product are obtained.
Reaction SMILES: [CH:1]1[C:6]([C@H:7]2[C@H:12]([CH2:13][O:14][C:15]3[CH:16]=[CH:17][C:18]4[O:23][CH2:22][O:21][C:19]=4[CH:20]=3)[CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:5][CH:4]=[C:3](F)[CH:2]=1.[CH3:25][S:26]([OH:29])(=[O:28])=[O:27].CCCCCC>CC(O)C>[CH3:25][S:26]([OH:29])(=[O:28])=[O:27].[CH2:8]1[C@@H:7]([C:6]2[CH:1]=[CH:2][CH:3]=[CH:4][CH:5]=2)[C@H:12]([CH2:13][O:14][C:15]2[CH:16]=[CH:17][C:18]3[O:23][CH2:22][O:21][C:19]=3[CH:20]=2)[CH2:11][NH:10][CH2:9]1
Reactant: Fc1ccc([C@@H]2CCNC[C@H]2COc2ccc3c(c2)OCO3)cc1
Agent: CS(=O)(=O)O
Solvent: CCCCCC
Solvent: CC(C)O
Product: c1ccc([C@@H]2CCNC[C@H]2COc2ccc3c(c2)OCO3)cc1
Temperature: 50 °C

Procedure:
To a stirred solution of paroxetine base (20.9 g) in propan-2-ol (70 ml) was added methanesulfonic acid (3.7 ml) in propan-2-ol (10 ml). The solution was heated to 50° C. and added portion-wise to hexane (200 ml) also at 50° C. The solution was stirred vigorously to form a precipitate which was stirred further to ensure crystallisation. The precipitate was collected by filtration, washed with hexane (40 ml) and dried in a vacuum desiccator over phosphorus pentoxide to give paroxetine methanesulfonate as a white crystalline solid.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2.C([O-])([O-])=O.[K+].[K+].[CH2:19](Br)[CH:20]=[CH2:21]>CN(C=O)C>[CH2:21]([O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2)[CH:20]=[CH2:19]
Reactant: C=CCBr
Reactant: O=C1CCc2cc(O)ccc2N1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C=CCOc1ccc2c(c1)CCC(=O)N2
Temperature: 25 °C
Reaction time: 3 h
Yield: 91 %

Procedure:
To a solution of 6-hydroxy-3,4-dihydroquinolin-2(1H)-one (1.5 g, 9.19 mmol) in DMF (20 mL), K2CO3 (2.54 g, 18.39 mmol) and allyl bromide (0.955 mL, 11.03 mmol) were added. The reaction mixture was stirred at room temperature for 3 h then concentrated. The residue was dissolved in ethyl acetate, washed with 10% NaOH solution, water, and brine. The organic layer was dried over anhydrous sodium sulfate, and concentrated to give 6-(allyloxy)-3,4-dihydroquinolin-2(1H)-one as a white solid (1.7 g, 89%). 1HNMR: 400 MHz, DMSO-d6: δ 2.40 (q, J=7.60 Hz, 2H), 2.83 (t, J=8.00 Hz, 2H), 4.48-4.50 (m, 2H), 5.22-5.26 (m, 1H), 5.35-5.40 (m, 1H), 5.97-6.07 (m, 1H), 6.72-6.80 (m, 3H), 9.89 (s, 1H), LCMS (ES-API), RT 1.566 min, m/z 204.2 (M+H).