Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:8]([Cl:9])=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].C([O-])(=O)C.[K+].C(OC(=O)C)(=O)C.[N:22](OCCC(C)C)=O.[Li+].[OH-]>O.C1COCC1.C(Cl)(Cl)Cl>[Cl:9][C:8]1[CH:7]=[CH:6][CH:5]=[C:3]2[C:2]=1[CH:1]=[N:22][NH:4]2
Reactant: Cc1c(N)cccc1Cl
Reactant: CC(C)CCON=O
Agent: CC(=O)[O-]
Agent: [K+]
Agent: [Li+]
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Solvent: CC(=O)OC(C)=O
Product: Clc1cccc2[nH]ncc12
Temperature: 0 °C

Procedure:
To a 250 ml flask with stirbar was added 2-methyl-3-chloroaniline (8.4 ml, 9.95 g, 70.6 mmol), potassium acetate (8.3 g, 84.7 mmol) and chloroform (120 ml). This mixture was cooled to 0° C. with stirring. To the cooled mixture was added acetic anhydride (20.0 ml, 212 mmol) drop wise over 2 minutes. The reaction mixture was warmed to 25° C. and stirred for 1 hour. At this point, the reaction was heated to 60° C. Isoamyl nitrite (18.9 ml, 141 mmol) was added and the reaction was stirred overnight at 60° C. Once complete, water (75 ml) and THF (150 ml) were added and the reaction was cooled to 0° C. LiOH (20.7 g, 494 mmol) was added and the reaction was stirred at 0° C. for 3 hours. Water (200 ml) was added and the product was extracted with EtOAc (300 ml, 100 ml). The organic layers were combined, dried with MgSO4 and concentrated in vacuo to yield 11.07 g (100%) as an orange solid. 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J=1 Hz, 1H), 7.33 (d, J=8 Hz, 1H), 7.31 (t, J=7 Hz, 1H), 7.17 (dd, J=7 Hz, 1 Hz 1H). LCMS (ESI pos) m/e 153 (M+1).
Reaction SMILES: [C:1]1([C:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([CH:27]=[CH2:28])=[CH:23][CH:22]=4)[N:17]=3)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C=C(Cl)C=C(C(OO)=[O:37])C=1>C(Cl)Cl>[O:37]1[CH2:28][CH:27]1[C:24]1[CH:23]=[CH:22][C:21]([C:18]2[N:17]=[C:16]([C:10]3[O:9][N:8]=[C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[C:11]=3[C:12]([F:13])([F:14])[F:15])[O:20][N:19]=2)=[CH:26][CH:25]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: C=Cc1ccc(-c2noc(-c3onc(-c4ccccc4)c3C(F)(F)F)n2)cc1
Solvent: ClCCl
Product: FC(F)(F)c1c(-c2ccccc2)noc1-c1nc(-c2ccc(C3CO3)cc2)no1
Temperature: 25 °C
Reaction time: 8 h
Yield: 97.6 %

Procedure:
To a mixture of 5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-3-(4-vinylphenyl)-1,2,4-oxadiazole (1.200 g, 3.13 mmol) in DCM (50 mL) was added m-CPBA (1.754 g, 7.83 mmol) in portions. The mixtures were allowed to stir at room temperature overnight. The reaction mixture was diluted with 100 ml DCM and washed with 1N NaOH. The organic layer was then dried and concentrated to provide 1.22 g of product as white solid. MS (m+1)=400. HPLC Peak RT=2.13 minutes. The two enantiomers were separated using the conditions below: Berger SFC MGIII instrument equipped with a Whelk-O 1 (25×3 cm, 5 μm). Wavelength 250 nm; Temp 35° C.; Flow rate: 150 mL/min; Mobile phase: CO2/(MeOH+0.1% DEA) in 4:1 ratio isocratic: RT=8.6 min for Peak 1 and 10.1 min for Peak 2. The absolution stereochemistry of the peak 1 (Isomer A) compound was unambiguously assigned as (S)-3-(4-(oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole by treating it with (S)-ethyl piperidine-3-carboxylate using the procedure found in Example 26 followed by deprotection of the ester using the procedure found in Example 14 to provide Example 14. This product matched Example 14 by 1H NMR and chiral HPLC.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[OH:9])=[CH:4][CH:3]=1.[Cl:23][CH2:24][CH2:25][CH2:26][C:27]([N:29]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:28].C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+].[ClH:50]>CN(C)C=O.O>[OH2:9].[ClH:23].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)([OH:9])[CH:10]2[CH2:11][CH2:12][N:13]([CH2:24][CH2:25][CH2:26][C:27]([N:29]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)=[O:28])[CH2:14][CH2:15]2)=[CH:4][CH:3]=1.[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH:10]2[CH2:11][CH2:12][N:13]([CH2:24][CH2:25][CH2:26][C:27]([N:29]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)=[O:28])[CH2:14][CH2:15]2)([OH:9])[C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)=[CH:4][CH:3]=1.[ClH:50]
Reactant: O=C(CCCCl)N(c1ccccc1)c1ccccc1
Reactant: OC(c1ccc(F)cc1)(c1ccc(F)cc1)C1CCNCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: O
Solvent: CN(C)C=O
Product: O=C(CCCN1CCC(C(O)(c2ccc(F)cc2)c2ccc(F)cc2)CC1)N(c1ccccc1)c1ccccc1
Yield: 29 %

Procedure:
A mixture of 6.1 g (0.020 mole) of α,α-bis(4-fluorophenyl)-4-piperidinemethanol, 6.8 g (0.025 mole) of 4-chloro-N,N-diphenylbutanamide, 8.5 g (0.080 mole) of anhydrous sodium carbonate and 0.3 g (0.002 mole) of potassium iodide in 100 mL of N,N-dimethylformamide was heated on a steam bath for 16 h. The mixture was poured into 2 L of water and extracted thrice with 250 mL portions of ethyl acetate. The ethyl acetate fractions were combined, washed with water and brine, dried (MgSO4) and concentrated under reduced pressure to give a viscous oil. The oil was purified by column chromatography using 250 g of silica gel on a 65 cm×4 cm column, eluted with ethyl acetate. The fractions containing the desired product were combined and concentrated under reduced pressure to give a glass. The glass was converted to the hydrochloric acid salt and the solid was recrystallized from ethyl acetate/ethyl ether to yield 3.3 g (29%) of white solid, mp 130°-132° C.
Reaction SMILES: CS(O[CH2:6][CH2:7][CH:8]([C:12]([F:15])([F:14])[F:13])[CH:9]([CH3:11])[CH3:10])(=O)=O.[F:16][C:17]([F:29])([F:28])[CH2:18][CH2:19][S:20]([CH2:23][C:24]([O:26][CH3:27])=[O:25])(=[O:22])=[O:21].C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O>[CH3:11][CH:9]([CH3:10])[CH:8]([C:12]([F:13])([F:14])[F:15])[CH2:7][CH2:6][CH:23]([S:20]([CH2:19][CH2:18][C:17]([F:28])([F:29])[F:16])(=[O:22])=[O:21])[C:24]([O:26][CH3:27])=[O:25]
Reactant: CC(C)C(CCOS(C)(=O)=O)C(F)(F)F
Reactant: COC(=O)CS(=O)(=O)CCC(F)(F)F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: COC(=O)C(CCC(C(C)C)C(F)(F)F)S(=O)(=O)CCC(F)(F)F
Temperature: 60 °C
Reaction time: 72 h
Yield: 52.9 %

Procedure:
To a solution of 5.0 g of 4-methyl-3-(trifluoromethyl)pentyl methanesulfonate and 4.7 g of methyl (3,3,3-trifluoropropylsulfonyl)acetate in 100 ml of dimethyl sulfoxide was added 2.8 g of potassium carbonate at room temperature. The reaction mixture was heated to 60° C., stirred at the same temperature for 3 days and then allowed to stand to cool to nearly room temperature. To the reaction mixture was added 10% hydrochloric acid, and then extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography to obtain 4.10 g of methyl 6-methyl-5-(trifluoromethyl)-2-(3,3,3-trifluoropropylsulfonyl)heptanoate (hereinafter referred to as the present compound (18)).
Reaction SMILES: C1(C)C(S(O[C:11]2[C:21]([O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:20][CH:19]=[CH:18][C:12]=2[CH:13]([CH3:17])[C:14]([OH:16])=[O:15])(=O)=O)=CC=CC=1.[H][H]>[Ni]>[O:22]([C:21]1[CH:11]=[C:12]([CH:18]=[CH:19][CH:20]=1)[CH:13]([CH3:17])[C:14]([OH:16])=[O:15])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: Cc1ccccc1S(=O)(=O)Oc1c(Oc2ccccc2)cccc1C(C)C(=O)O
Reactant: [H][H]
Agent: [Ni]
Product: CC(C(=O)O)c1cccc(Oc2ccccc2)c1
Yield: 89 %

Procedure:
To a solution of 4.1 g. of 2-toluene-sulphonyloxy-3-phenoxy-hydratropic acid in 150 ml. of alcohol 24 g. of a W-6 nickel catalyst are added, and the mixture is hydrogenated at 25° C., under atmospheric pressure until a calculated amount of hydrogen is used up. The catalyst is filtered off, the filtrate is evaporated and the residue is taken up in water and acidified with a 10% aqueous hydrochloric acid solution. The separated oil is extracted with chloroform, the chloroform solution is dried over sodium sulphate and evaporated. 2.1 g. (89%) of 3-phenoxy-hydratropic acid are obtained. Melting point of the corresponding cyclohexylamine salt amounts to 151° C. to 153° C.
Reaction SMILES: [N+]([O-])([O-])=O.[Pd+2:5].[N+]([O-])([O-])=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[OH:19][S:20]([C:23]([F:26])([F:25])[F:24])(=[O:22])=[O:21]>>[O-:22][S:20]([C:23]([F:26])([F:25])[F:24])(=[O:21])=[O:19].[Pd+2:5].[O-:22][S:20]([C:23]([F:26])([F:25])[F:24])(=[O:21])=[O:19]
Reactant: O=S(=O)(O)C(F)(F)F
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=[N+]([O-])[O-]
Product: O=S(=O)([O-])C(F)(F)F

Procedure:
Palladium triflate [Pd(Tfo)2 ] was prepared from wet palladium (II) nitrate [Pd(NO3)2 ] or palladium (II) acetate [Pd(AcO)2 ] with excess of triflic acid [TfOH] at room temperature (typically about 18 to about 30° C.). The liquid was evaporated from the reaction mixture under vacuum at 150 ° C and dry palladium triflate was obtained and stored under inert gas for further use as a catalyst in the aryl coupling reactions.
Reaction SMILES: C(OC(=O)[N:7]([C:28]1[CH:33]=[CH:32][C:31]([CH2:34][CH2:35][CH2:36][CH2:37][N:38]2[CH:42]=[CH:41][N:40]=[N:39]2)=[CH:30][CH:29]=1)[CH2:8][C:9]1[N:10]=[C:11]([CH:14]=[CH:15][C:16]2[CH:21]=[CH:20][C:19]([S:22]([F:27])([F:26])([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)[O:12][CH:13]=1)(C)(C)C.O.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.FC(F)(F)C(O)=O>[N:38]1([CH2:37][CH2:36][CH2:35][CH2:34][C:31]2[CH:30]=[CH:29][C:28]([NH:7][CH2:8][C:9]3[N:10]=[C:11]([CH:14]=[CH:15][C:16]4[CH:17]=[CH:18][C:19]([S:22]([F:27])([F:26])([F:23])([F:24])[F:25])=[CH:20][CH:21]=4)[O:12][CH:13]=3)=[CH:33][CH:32]=2)[CH:42]=[CH:41][N:40]=[N:39]1
Reactant: CC(C)(C)OC(=O)N(Cc1coc(C=Cc2ccc(S(F)(F)(F)(F)F)cc2)n1)c1ccc(CCCCn2ccnn2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: FS(F)(F)(F)(F)c1ccc(C=Cc2nc(CNc3ccc(CCCCn4ccnn4)cc3)co2)cc1
Yield: 26.4 %

Procedure:
A solution of 450 mg (0.72 mmol) [4-(4-[1,2,3]triazol-1-yl-butyl)-phenyl]-{2-[2-(4-pentafluorosulfanyl-phenyl)-vinyl]-oxazol-4-ylmethyl}-carbamic acid tert-butyl ester in 4 ml dichloromethane and 4 ml trifluoroacetic acid was stirred at r.t. for 1 h. Water was added and the mixture neutralized with solid sodium carbonate. The organic phase was separated, washed with water, dried over sodium sulfate and evaporated. The residue was stirred with a little isopropanol, the crystallized material isolated by filtration, washed with ether and dried to give 100 mg (27%) of product.
Reaction SMILES: [C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].[NH3:9]>>[NH2:9][C@H:2]([C:1]([OH:8])=[O:7])[CH2:3][C:4]([OH:6])=[O:5]
Reactant: N
Reactant: O=C(O)/C=C/C(=O)O
Product: N[C@@H](CC(=O)O)C(=O)O

Procedure:
The cultures of H-9183 strain as obtained in Example 1 were suitably diluted, to which was added fumaric acid to the concentration of 100 g/liter. Then, ammonia was added thereto to adjust the pH at 8.7. The reaction was carried out at 30° C. with gently stirring.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([Cl:11])(=[O:10])=[O:9])=[CH:4][CH:3]=1.II.[Cl:14]Cl>[Fe](Cl)(Cl)Cl>[Cl:14][C:3]1[CH:4]=[C:5]([S:8]([Cl:11])(=[O:10])=[O:9])[CH:6]=[CH:7][C:2]=1[CH3:1]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: ClCl
Agent: Cl[Fe](Cl)Cl
Agent: II
Product: Cc1ccc(S(=O)(=O)Cl)cc1Cl

Procedure:
576 g (3 mol) of 4-methylbenzenesulfonyl chloride are melted in a chlorination apparatus. After addition of 7 g of iron(III) chloride and 2 g of iodine, elemental chlorine is passed in (5 l Cl2 /h) at from 75° to 80° C. until 100% chlorination is achieved (GC analysis).
Reaction SMILES: [Cl:1][C:2]1[C:13]([Cl:14])=[C:12]([C:15](=[O:20])[C:16](=[CH2:19])[CH2:17][CH3:18])[CH:11]=[CH:10][C:3]=1[O:4][CH2:5][CH2:6][C:7]([OH:9])=[O:8].O.C(=O)(O)[O-].[Na+:26]>>[Cl:1][C:2]1[C:13]([Cl:14])=[C:12]([C:15](=[O:20])[C:16](=[CH2:19])[CH2:17][CH3:18])[CH:11]=[CH:10][C:3]=1[O:4][CH2:5][CH2:6][C:7]([O-:9])=[O:8].[Na+:26]
Reactant: C=C(CC)C(=O)c1ccc(OCCC(=O)O)c(Cl)c1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: C=C(CC)C(=O)c1ccc(OCCC(=O)[O-])c(Cl)c1Cl

Procedure:
25 mg of 3-[2,3-dichloro-4-(2-methylenebutyryl)phenoxy]propionic acid is dissolved in 3.1 ml of 0.1N sodium bicarbonate and sufficient isotonic buffer to make a final volume of 10 ml. The water from all sources was pyrogen-free. The solution is sterilized by filtration.
Reaction SMILES: [CH2:1]([C:3]1[CH2:4][CH:5]2[CH:8]([CH:9]=1)[C:7]([CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])([CH2:10][N+:11]([O-])=O)[CH2:6]2)[CH3:2].[H][H]>[Ni].C(O)C>[NH2:11][CH2:10][C:7]1([CH2:14][C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:6][CH:5]2[CH:8]1[CH:9]=[C:3]([CH2:1][CH3:2])[CH2:4]2
Reactant: [H][H]
Reactant: CCC1=CC2C(C1)CC2(CC(=O)OC(C)(C)C)C[N+](=O)[O-]
Agent: [Ni]
Solvent: CCO
Product: CCC1=CC2C(C1)CC2(CN)CC(=O)OC(C)(C)C
Yield: 92 %

Procedure:
Raney nickel (96 mg, 0.16 w/w) and ethanol (200 μL) were added to tert-butyl [3-ethyl-6-(nitromethyl)bicyclo[3.2.0]hept-3-en-6-yl]acetate (59 mg, 85:15 diastereomeric mixture), and the mixture was stirred at room temperature for 12 hours under the hydrogen atmosphere. The Raney nickel was filtered off. Then, the solvent was distilled off to obtain the compound of interest as a brown oil substance (49 mg, yield: 92%, 85:15 diastereomeric mixture).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[CH2:5][S:6][C:7]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:8]=1[C:9]([OH:11])=[O:10].NO[C:25]1CCCCCC=1>C(OCC)C>[CH3:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[CH2:5][S:6][C:7]1[CH:15]=[CH:14][C:13]([C:16]([F:17])([F:18])[F:19])=[CH:12][C:8]=1[C:9]([O:11][CH3:25])=[O:10]
Reactant: Cc1cccc(CSc2ccc(C(F)(F)F)cc2C(=O)O)c1
Reactant: NOC1=CCCCCC1
Solvent: CCOCC
Product: COC(=O)c1cc(C(F)(F)F)ccc1SCc1cccc(C)c1

Procedure:
A mixture of 2-(m-methylbenzylthio)-5-trifluoromethylbenzoic acid (1.65 g, 5.06 mmol) and 1-aza-2-methoxy-1-cycloheptene (643 mg, 5.06 mmol) was heated at 80°-85° C. for 18 hours, cooled, diluted with diethyl ether, washed with 1N aqueous sodium hydroxide solution, water, dried (sodium sulfate), and evaporated. The product was crystallized from methanol; yield 885 mg (51%). The 60 MHz NMR spectrum in chloroform-d was in accord with the desired structure.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]([C:17]1[CH:18]=[N:19][C:20]([N:23]2[CH2:28][CH2:27][N:26]([CH2:29][CH3:30])[CH2:25][CH2:24]2)=[CH:21][CH:22]=1)=[O:16].C(=O)([O-])O.[Na+].[N+:36]([O-])([OH:38])=[O:37]>>[O:1]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]([C:17]1[CH:18]=[N:19][C:20]([N:23]2[CH2:28][CH2:27][N:26]([CH2:29][CH3:30])[CH2:25][CH2:24]2)=[CH:21][CH:22]=1)=[O:16])[N+:36]([O-:38])=[O:37]
Reactant: O=[N+]([O-])O
Reactant: CCN1CCN(c2ccc(C(=O)NCCCCCCCCCCCCO)cn2)CC1
Agent: O=C([O-])O
Agent: [Na+]
Product: CCN1CCN(c2ccc(C(=O)NCCCCCCCCCCCCO[N+](=O)[O-])cn2)CC1
Temperature: -25 °C
Reaction time: 0.67 h

Procedure:
To 30 ml of fuming nitric acid cooled to -30° C. was gradually added 7.9 g of N-(12-hydroxydodecyl)-6-(4-ethyl-1-piperazinyl)pyridine-3-carboxamide over 30 minutes and the mixture was stirred at -30 to -20° C. for 40 minutes. The reaction solution was poured into ice, neutralized with sodium hydrogen carbonate and extracted with chloroform. The extract was dried over anhydrous sodium sulfate and distilled under reduced pressure. The residue thus obtained was chromatographed over a silica gel column and recystallized from methanol-water to afford the title compound as a crystal.
Reaction SMILES: [OH:1][C:2]1[CH:15]=[CH:14][C:5]([C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1.[OH-].[Na+].[Br:18][CH2:19][CH2:20][CH2:21][CH2:22]Br>CCCCC>[Br:18][CH2:19][CH2:20][CH2:21][CH2:22][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:7])=[CH:14][CH:15]=1
Reactant: BrCCCCBr
Reactant: O=C(c1ccccc1)c1ccc(O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCCCC
Product: O=C(c1ccccc1)c1ccc(OCCCCBr)cc1
Temperature: 25 °C
Reaction time: 20.5 h

Procedure:
Combine 4-hydroxybenzophenone (14.11 g, 71.2 mmol) and aqueous 1M sodium hydroxide solution (70 mL). Add 1,4-dibromobutane (43.4 g, 200 mmol). Heat the reaction mixture to reflux. After 20.5 hours, cool to ambient temperature. Add pentane (100 mL) and again heat to reflux. After 0.5 hours, cool to ambient temperature to give a solid. Collect the solid by filtration recrystallize the solid from ethanol to give the title compound: mp; 42°-43° C.
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]([N+:25]([O-])=O)[CH:16]=2)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]>CO.[Pd]>[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]([NH2:25])[CH:16]=2)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2cc([N+](=O)[O-])cc(C(F)(F)F)c2)CC1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC(Oc2cc(N)cc(C(F)(F)F)c2)CC1

Procedure:
1-Boc-4-(3-nitro-5-trifluoromethyl-phenoxy)-piperidine (470 mg) was dissolved in MeOH (12 ml) and Pd/C (10 mg) was added. After sparging briefly with H2, the mixture was stirred under H2 for 6 H. The catalyst was removed by filtration and the MeOH solution was concentrated in vacuo to yield 1-Boc-4-(3-amino-5-trifluoromethyl-phenoxy)-piperidine as an off-white foam.
Reaction SMILES: C(S(C1N(CC(=O)CCC2C=CC=CC=2)C(=O)C1)=O)(C)(C)C.[CH2:23]([S:29]([CH:31]1[N:34]([CH2:35][C:36](=[O:45])[CH2:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:33](=[O:46])[CH2:32]1)=[O:30])[CH2:24][CH2:25][CH2:26]CC.C1(CCCCCCNC(=O)CN2C(S(C)=O)CC2=O)C=CC=CC=1>>[CH2:23]([S:29]([CH:31]1[N:34]([CH2:35][C:36](=[O:45])[CH2:37][CH2:38][C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[C:33](=[O:46])[CH2:32]1)=[O:30])[CH2:24][CH2:25][CH3:26]
Reactant: CCCCCCS(=O)C1CC(=O)N1CC(=O)CCc1ccccc1
Agent: CC(C)(C)S(=O)C1CC(=O)N1CC(=O)CCc1ccccc1
Agent: CS(=O)C1CC(=O)N1CC(=O)NCCCCCCc1ccccc1
Product: CCCCS(=O)C1CC(=O)N1CC(=O)CCc1ccccc1

Procedure:
4-tert-Butylsulfinyl-1-(4-phenyl-2-oxobutyl)azetidin-2-one;4-n-Hexylsulfinyl-1-(4-phenyl-2-oxobutyl)azetidin-2-one;N-6-Phenylhexyl-(4-methylsulphinyl-2-oxoazetidin-1-yl)acetamide;
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH3:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=1.[CH:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][C:17]=1[O:26][CH2:27][CH2:28][CH2:29]Cl>CS(C)=O.O>[CH3:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][CH2:29][CH2:28][CH2:27][O:26][C:17]2[CH:18]=[CH:19][C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:16]=2)=[CH:11][CH:10]=1
Reactant: ClCCCOc1ccc2ccccc2c1
Reactant: COc1ccc(N)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: COc1ccc(NCCCOc2ccc3ccccc3c2)cc1
Temperature: 140 °C

Procedure:
A mixture of anhydrous potassium carbonate (10 gm, in excess) and p-anisidine (0.42 gm, 0.003 mole) was taken in dry DMSO (40 ml). Now 3-(2-naphthyloxy)-1-chloropropane (0.5 gm, 0.002 mole) was added in it. Reaction mixture was refluxed at 140° C. for 7 hrs and the reaction was completed as checked by TLC. Reaction mixture was poured in distilled water (60 ml) and extracted with ethyl acetate thrice. The organic layer was separated and concentrated to get oily compound which was later crystallized by benzene hexane to get N-(4-methoxyphenyl)-[3-(naphthalen-2-yloxy)propyl]amine as yellow solid, m.p. 110° C., (yield 0.66 gm, 95.6%).
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:7][C:6]2[C:8]([O:13][CH3:14])=[CH:9][CH:10]=[C:11]([F:12])[C:5]=2[O:4][CH2:3]1.[C:15]1(=O)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.CC(O)=O.[BH3-]C#N.[Na+]>CO>[CH:15]1([NH:1][C@@H:2]2[CH2:7][C:6]3[C:8]([O:13][CH3:14])=[CH:9][CH:10]=[C:11]([F:12])[C:5]=3[O:4][CH2:3]2)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: COc1ccc(F)c2c1C[C@@H](N)CO2
Reactant: O=C1CCCCC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: COc1ccc(F)c2c1C[C@@H](NC1CCCCC1)CO2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of (R)-3-amino-8-fluoro-5-methoxy-3,4-dihydro-2H-1-benzopyran (0.45 g, 2.2 mmol), cyclohexanone (0.7 g, 7.2 mmol) and HOAc (0.14 g, 2.3 mmol) in methanol (25 mL) was NaCNBH3 (0.5 g, 8 mmol) added in portions at room temperature. The solution was stirred at room temperature overnight to give a quantitative yield of the title compound. GC/MS (70 eV) M=279 (30%).
Reaction SMILES: [C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]([CH2:13][CH2:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH2:5]1)(=[O:3])[CH3:2].[Br:19]Br>C(O)(=O)C.ClCCl>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([Br:19])=[CH:10][CH:11]=2)[CH:6]([CH2:13][CH2:14][S:15]([CH3:18])(=[O:16])=[O:17])[CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1CC(CCS(C)(=O)=O)c2ccccc21
Reactant: BrBr
Solvent: ClCCl
Solvent: CC(=O)O
Product: CC(=O)N1CC(CCS(C)(=O)=O)c2cc(Br)ccc21

Procedure:
Bromination was done by treatment of 19a with bromine in a mixture of acetic acid and dichloromethane. The compound was an oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]2[CH:9]=[CH:10][NH:11][C:6]2=[CH:5][CH:4]=1.[OH-].[K+].O.Cl.[NH:16]1[CH2:21][CH2:20][C:19](=O)[CH2:18][CH2:17]1>>[CH3:1][O:2][C:3]1[N:8]=[C:7]2[C:9]([C:19]3[CH2:20][CH2:21][NH:16][CH2:17][CH:18]=3)=[CH:10][NH:11][C:6]2=[CH:5][CH:4]=1
Reactant: O=C1CCNCC1
Reactant: COc1ccc2[nH]ccc2n1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: COc1ccc2[nH]cc(C3=CCNCC3)c2n1
Yield: 67.8 %

Procedure:
A solution of 0.20 gm (1.35 mMol) of 5-methoxypyrrolo-[3,2-b]pyridine, 0.23 mg (4.05 mMol) potassium hydroxide, and 0.31 gm (2.03 mMol) 4-piperidone hydrochloride monohydrate 5 mL methanol was heated at reflux for 18 hours. The reaction mixture was then concentrated under reduced pressure and the residue partitioned between water and 3:1 chloroform:isopropanol. The organic phase was washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to radial chromatography chromatography (2 mm silica gel plate) eluting with dichloromethane containing 20-40% methanol and 1% ammonium hydroxide. Fractions containing product were combined and concentrated under reduced pressure to provide 0.21 gm (68%) of the title compound as a yellow sold. An analytical sample was crystallized from methanol.
Reaction SMILES: C(OC([NH:8][C@@H:9]1[CH2:13][C@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@@H:11]([CH2:20][N:21]2[CH2:26][CH2:25][CH:24]([N:27]([C:31]([O:33][CH2:34][C:35]3[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=3)=[O:32])[CH2:28][CH:29]=[CH2:30])[CH2:23][CH2:22]2)[CH2:10]1)=O)(C)(C)C.[CH3:44][N:45]=[C:46]=[S:47]>>[CH3:44][NH:45][C:46]([NH:8][C@@H:9]1[CH2:13][C@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@@H:11]([CH2:20][N:21]2[CH2:22][CH2:23][CH:24]([N:27]([C:31]([O:33][CH2:34][C:35]3[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=3)=[O:32])[CH2:28][CH:29]=[CH2:30])[CH2:25][CH2:26]2)[CH2:10]1)=[S:47]
Reactant: C=CCN(C(=O)OCc1ccc([N+](=O)[O-])cc1)C1CCN(C[C@H]2C[C@H](NC(=O)OC(C)(C)C)C[C@@H]2c2ccccc2)CC1
Reactant: CN=C=S
Product: C=CCN(C(=O)OCc1ccc([N+](=O)[O-])cc1)C1CCN(C[C@H]2C[C@H](NC(=S)NC)C[C@@H]2c2ccccc2)CC1

Procedure:
Using essentially the same procedure as in Example 16, Step A and B but substituting 1-(R)-((t-butoxycarbonyl)amino)-3-(S)-((4-(N-(4-nitrobenzyloxycarbonyl)-N-(allyl)amino)piperidin-1-yl)methyl)-4-(S)-phenylcyclopentane from Example 34 in Step A and methyl isothiocyanate in Step B, the title compound was prepared.