Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.[OH:10]/[N:11]=[C:12](/[C:18](=[O:20])[CH3:19])\[C:13]([O:15][CH2:16][CH3:17])=[O:14]>FC(F)(F)S([O-])(=O)=O.[Ag+]>[C:2]12([O:10]/[N:11]=[C:12](/[C:18](=[O:20])[CH3:19])\[C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][CH2:3]2
Reactant: CCOC(=O)/C(=N\O)C(C)=O
Reactant: BrC12CCC(CC1)CC2
Agent: [Ag+]
Agent: O=S(=O)([O-])C(F)(F)F
Product: CCOC(=O)/C(=N\OC12CCC(CC1)CC2)C(C)=O
Yield: 22.6 %

Procedure:
1-Bromobicyclo[2.2.2]octane (4.6 g, 24.3 mmol), ethyl (Z)-2-hydroxyimino-3-oxobutyrate (3.78 g, 24.3 mmol) and silver trifluoromethanesulphonate (6.32 g, 24.6 mmol) were reacted under similar conditions to that described in Example 31a to give the title compound (1.47 g, 22%); νmax (CH2Cl2) 2950, 2925, 2860, 1735, 1685, 1370 and 1325 cm-1 ; δH (60 MHz, CDCl3) 1.30 (3H, t, J ca 7 Hz), 1.64 (S) and 1.75 (s) (together 13H), 2.36 (3H, s), and 4.30 (2H, q); [Ammonia CI mass spectrum Found MH+ (288)].
Reaction SMILES: [H-].[Na+].[NH2:3][CH:4]([CH3:7])[CH2:5][OH:6].[Cl:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11](Cl)[N:10]=1>C1COCC1>[Cl:8][C:9]1[N:10]=[C:11]([O:6][CH2:5][CH:4]([NH2:3])[CH3:7])[CH:12]=[CH:13][CH:14]=1
Reactant: CC(N)CO
Reactant: Clc1cccc(Cl)n1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(N)COc1cccc(Cl)n1
Reaction time: 0.5 h
Yield: 84.2 %

Procedure:
Sodium hydride (60 wt. percent oil dispersion, 560 mg, 14 mmol) was added to a stirred solution of 2-aminopropanol (1.2 mL, 14 mmol) in THF (25 mL). After 30 minutes, 2,6-dichloropyridine (2.0 g, 14 mmol) was added and the reaction heated at reflux for 8 hours. After cooling, the reaction was quenched with aqueous 1N hydrochloric acid and washed with ether (3×30 mL). The pH of the aqueous phase was then raised to 10-11 with 50 wt. percent aqueous sodium hydroxide and extracted with ether (3×50 mL). The organics were dried (MgSO4), filtered and solvent removed in vacuo leaving 2.2 g of a yellow oil.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:7]=1[N+:8]([O-:22])=[C:9]1[C:14](=[N+:15]2[O-:20])[C:13]([OH:21])=[CH:12][CH:11]=[CH:10]1.[NH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1>C(Cl)(Cl)Cl>[N:23]1([CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:7]=2[N+:8]([O-:22])=[C:9]2[C:14](=[N+:15]3[O-:20])[C:13]([OH:21])=[CH:12][CH:11]=[CH:10]2)[CH2:27][CH2:26][CH2:25][CH2:24]1
Reactant: C1CCNC1
Reactant: [O-][n+]1c2cccc(OCCCCl)c2[n+]([O-])c2cccc(O)c21
Solvent: ClC(Cl)Cl
Product: [O-][n+]1c2cccc(OCCCN3CCCC3)c2[n+]([O-])c2cccc(O)c21
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
2.0 grams of 6-(3-chloropropoxy)-1-phenazinol 5,10-dioxide and 20ml of pyrrolidine were placed in a flask and stirred at room temperature for 3 1/2 hours. The reaction mixture was diluted with CHCl3 and washed repeatedly with water until the water washes were neutral. The chloroform solution was extracted with 3 × 150 ml of 10 percent aqueous HCl. The acid extracts were combined, neutralized with sodium carbonate, extracted with CHCl3 and the combined CHCl3 extracts were washed with water and dried over sodium sulfate and concentrated in vacuo. The residue was recrystallized from acetone. The solids were filtered and washed with a little ether and dried in vacuo at 50° for 16 hours to yield metallic red crystals of 6-(3-pyrrolidinopropoxy)-1-phenazinol 5,10-dioxide, m.p. 113°-114°C (dec.).
Reaction SMILES: [Cl:1][C:2]1[C:7](Cl)=[CH:6][C:5]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[C:4]([N+:16]([O-:18])=[O:17])[CH:3]=1.[Cl:19][C:20]1[CH:25]=[C:24]([Br:26])[C:23]([Cl:27])=[CH:22][C:21]=1[OH:28].[OH-].[Na+]>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([N+:16]([O-:18])=[O:17])[C:5]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][C:7]=1[O:28][C:21]1[CH:22]=[C:23]([Cl:27])[C:24]([Br:26])=[CH:25][C:20]=1[Cl:19]
Reactant: Oc1cc(Cl)c(Br)cc1Cl
Reactant: O=[N+]([O-])c1cc(Cl)c(Cl)cc1Oc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Product: O=[N+]([O-])c1cc(Cl)c(Oc2cc(Cl)c(Br)cc2Cl)cc1Oc1ccccc1
Temperature: 100 °C
Reaction time: 5 h

Procedure:
A mixture of 28.4 gm of 4,5-dichloro-2-nitro-1-phenoxy-benzene, 24.2 gm of 2,5-dichloro-4-bromo-phenol, 10 ml of 10 N sodium hydroxide and 80 ml of dimethylsulfoxide was stirred for 5 hours at 100° C. Thereafter, the reaction mixture was stirred into 700 ml of 1 N sodium hydroxide, the mixture was allowed to stand overnight at room temperature, the liquid phase was decanted, and the precipitated product was taken up in chloroform. The chloroform solution was washed with water, dried with sodium sulfate and evaporated, and the residue was recrystallized from a mixture of 200 ml ethanol and 2 ml dimethylformamide. 36.5 gm (75% of theory) of the light yellow crystalline title compound, m.p. 85° C., were obtained.
Reaction SMILES: C(O[C:4](=[O:19])[CH:5]([N:9]1[C:13]([CH3:14])=[N:12][C:11]([C:15]([F:18])([F:17])[F:16])=[N:10]1)[C:6](=O)[CH3:7])C.[NH2:20][NH2:21]>CCO>[CH3:7][C:6]1[C:5]([N:9]2[C:13]([CH3:14])=[N:12][C:11]([C:15]([F:16])([F:17])[F:18])=[N:10]2)=[C:4]([OH:19])[NH:20][N:21]=1
Reactant: NN
Reactant: CCOC(=O)C(C(C)=O)n1nc(C(F)(F)F)nc1C
Solvent: CCO
Product: Cc1n[nH]c(O)c1-n1nc(C(F)(F)F)nc1C
Temperature: 50 °C
Reaction time: 8 h

Procedure:
To a solution of 2-(5-methyl-3-trifluoromethyl-[1,2,4]triazol-1-yl)-3-oxo-butyric acid ethyl ester (890 mg, 3.19 mmol) in EtOH (15 ml) is added hydrazine (0.500 ml, 15.94 mmol) and the mixture left to stir at 50° C. overnight. The solvent is removed in vacuo and trituration of the resulting pale yellow oil with ether and EtOAc affords the title compound as a fine white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:17]=[CH:16][C:5]2[S:6][C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[C:9](=O)[NH:10][C:4]=2[CH:3]=1.P(Cl)(Cl)(Cl)=O.CN(C)C1C=CC=CC=1.[CH2:32]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)[CH3:33]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:17]=[CH:16][C:5]2[S:6][C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[C:9]([N:37]3[CH2:38][CH2:39][N:34]([CH2:32][CH3:33])[CH2:35][CH2:36]3)=[N:10][C:4]=2[CH:3]=1
Reactant: CCN1CCNCC1
Reactant: O=C1Nc2cc(Cl)ccc2Sc2ccccc21
Solvent: CN(C)c1ccccc1
Solvent: O=P(Cl)(Cl)Cl
Solvent: Cc1ccccc1
Product: CCN1CCN(C2=Nc3cc(Cl)ccc3Sc3ccccc32)CC1

Procedure:
8-Chloro-10H-dibenzo[b,f][1,4]thiazepin-11-one 2 (X=S and R1=Cl) (0.5 g, 1.91 mol), phosphorus oxychloride (5 ml, 53 mmol), toluene (25 ml) and N,N-dimethylaniline (1.0 ml) were heated at reflux for 3 hours. After evaporation of the volatiles, 25 ml of toluene and 5 ml (45 mmol) of 1-ethylpiperazine were added. Work-up and purification as described in Example 1 gave 150 mg (22%) of light yellow crystals, mp 100-101° C., 1H NMR (300 MHz, CDCl3), 1.11 (t, 3H, J=6.0 Hz, CH3), 2.55 (q, 2H, J=6.0 Hz, —CH2—), 2.55-2.65 (broad s, 4H, piperazinyl CH2), 3.55-3.65 (broad s, 4H, piperazinyl CH2), 6.83 (dd, 1H, J=1.5 and 6.0 Hz), 7.07 (d, 1H, J=1.5 Hz), 7.25-7.40 (mult., 4H), 7.50 (dd, 1H, J=7.5 Hz), MS (EI) m/z 357 (M+, 16.1%), 244(34.2), 209(30.1), 97(93.7), 84(100), HRMS calcd for C19H20N3SCl 357.1066, found 357.1067.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[S:7](=[O:11])(=O)(O)[OH:8].[CH2:12]([C@@:14]1([CH2:35][CH2:36][CH2:37][CH3:38])[C:20](=O)[N:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:18]2[CH:28]=[C:29]([Cl:34])[C:30]([O:32][CH3:33])=[CH:31][C:17]=2S[CH2:15]1)[CH3:13].[OH-].[Na+]>C(OCC)C.C1COCC1.O>[CH2:12]([C@:14]1([CH2:35][CH2:36][CH2:37][CH3:38])[CH2:20][N:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:18]2[CH:28]=[C:29]([Cl:34])[C:30]([O:32][CH3:33])=[CH:31][C:17]=2[S:7](=[O:11])(=[O:8])[CH2:15]1)[CH3:13]
Reactant: O=S(=O)(O)O
Reactant: CCCC[C@@]1(CC)CSc2cc(OC)c(Cl)cc2N(c2ccccc2)C1=O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: O
Product: CCCC[C@@]1(CC)CN(c2ccccc2)c2cc(Cl)c(OC)cc2S(=O)(=O)C1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a 1 M solution of lithium aluminum hydride in ethyl ether (91.5 ml) was added dropwise at 0° C. a 7.2 M solution of sulfuric acid in THF (6.4 ml) and the mixture was stirred at 0° C. for 1 h. To the mixture at 0° C. was added 8 (10.9 g) in THF (75 ml). The reaction mixture was allowed to warm to RT and stirred for 3.5 h at RT at which point it was cooled back to 0° C. and a 30% (v/v) solution of H2O in THF was added dropwise. A 1 N solution of NaOH (15 ml) was added. The reaction mixture was filtered through a sintered glass funnel to remove the aluminum oxides. The filtrate was transferred to a separatory funnel and partitioned between water and ethyl ether. The aqueous layer was extracted three times with ether. The organic phase was dried (Na2SO4) and concentrated. The resulting oil was taken up in THF (175 ml). To the THF solution was added t-butanol (60 ml), N-methyl-morpholine-N-oxide (10.7 g) and osmium tetraoxide (2.5 wt % in t-butanol, 7.6 ml). The reaction mixture was stirred for 18 h at RT. The reaction mixture was transferred to a separatory funnel and partitioned between brine and ethyl acetate. The aqueous layer was extracted three times with ethyl acetate. The organic layer was dried, concentrated and the residue applied to a silica gel column. The product was eluted with 10% ethyl acetate/petroleum ether giving 9 (10.92 g).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH3:16])[C:10]([N:12]([O:14][CH3:15])[CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N[C@@H](C(O)=O)C)(OC(C)(C)C)=O>>[C:1]([O:5][C:6]([NH:8][C@H:9]([CH3:16])[C:10]([N:12]([O:14][CH3:15])[CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CON(C)C(=O)[C@H](C)NC(=O)OC(C)(C)C
Agent: C[C@@H](NC(=O)OC(C)(C)C)C(=O)O
Product: CON(C)C(=O)[C@@H](C)NC(=O)OC(C)(C)C
Yield: 88 %

Procedure:
The title compound was prepared as (2S)-2-[(tert-butoxy)carbonylamino]-N-methoxy-N-methylpropanamide with boc-D-alanine (20 grams, 105.7 mmol) to give the title compound (21.7 g, 88%): ES-MS (m/z) 233.2 [M+1]+.
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[C:10]([N:11]3[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19]4[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[CH2:21][CH:20]=4)[CH2:13][CH2:12]3)[C:5]=2[O:4][CH2:3][CH2:2]1.Cl.C1(CC(O)=[O:40])C2C(=CC=CC=2)CC=1>>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[C:10]([N:11]3[CH2:12][CH2:13][N:14]([C:17](=[O:40])[CH2:18][C:19]4[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[CH2:21][CH:20]=4)[CH2:15][CH2:16]3)[C:5]=2[O:4][CH2:3][CH2:2]1
Reactant: C1=C(CCN2CCN(c3cccc4c3OCCO4)CC2)c2ccccc2C1
Reactant: O=C(O)CC1=CCc2ccccc21
Agent: Cl
Product: O=C(CC1=CCc2ccccc21)N1CCN(c2cccc3c2OCCO3)CC1
Yield: 30 %

Procedure:
4-(benzodioxan-5-yl)-1-[2-(ind-1-en-1-yl)-ethyl]-piperazine and its hydrochloride, m.p. (K): 254°-256° C., by reduction of 4-(benzodioxan-5-yl)-1-[2-(ind-1-en-1-yl)-acetyl]-piperazine (yield: 30%), which was itself prepared in a yield of 66% from 2-(ind-1-en-1-yl)acetic acid [m.p. (K): 92°-94° C.]and N-(benzodioxan-5-yl)piperazine.
Reaction SMILES: Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:17]=[CH:18][CH:19]=1)[CH2:6][CH:7]1[C:15](=[O:16])[N:10]2[CH2:11][CH2:12][NH:13][CH2:14][C@@H:9]2[CH2:8]1.[F:20][C:21]([F:33])([F:32])[C:22]1[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1.C(N(CC)CC)C>C(Cl)Cl>[F:2][C:3]1[CH:4]=[C:5]([CH:17]=[CH:18][CH:19]=1)[CH2:6][CH:7]1[C:15](=[O:16])[N:10]2[CH2:11][CH2:12][N:13]([S:28]([C:25]3[CH:24]=[CH:23][C:22]([C:21]([F:20])([F:32])[F:33])=[CH:27][CH:26]=3)(=[O:30])=[O:29])[CH2:14][C@@H:9]2[CH2:8]1
Reactant: O=C1C(Cc2cccc(F)c2)C[C@H]2CNCCN12
Reactant: O=S(=O)(Cl)c1ccc(C(F)(F)F)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C1C(Cc2cccc(F)c2)C[C@H]2CN(S(=O)(=O)c3ccc(C(F)(F)F)cc3)CCN12
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 93.9 %

Procedure:
The product from Example 213B (20 mg, 0.070 mmol) was suspended in CH2Cl2 (0.5 mL), 4-(trifluoromethyl)benzene-1-sulfonyl chloride (21 mg, 0.084 mmol) and triethylamine (0.049 mL, 0.35 mmol) were added, and the resulting mixture was stirred at room temperature for 90 minutes. The mixture was partitioned between water and CH2Cl2, and the organic layer was dried over Na2SO4. The drying agent was removed by filtration, and the filtrate was concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-5% CH3OH in CH2Cl2 to give the title compound (30 mg, 94%). 1H NMR (300 MHz, CDCl3) δ ppm 1.16-1.51 (m, 1H) 1.59-1.72 (m, 1H) 1.88-2.03 (m, 1H) 2.09-2.32 (m, 1H) 2.64-3.12 (m, 4H) 3.27-3.64 (m, 1H) 3.73-3.86 (m, 2H) 4.11 (dd, J=13.22, 2.37 Hz, 1H) 6.68-6.98 (m, 3H) 7.08-7.29 (m, 1H) 7.77-7.89 (m, 4H); MS (ESI) m/z 457 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:31])=[C:4]([CH:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][CH:9]2[C:28]([OH:30])=O)[CH:5]=[CH:6][CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:65][S:66][C:67]1[CH:72]=[CH:71][C:70]([NH2:73])=[CH:69][CH:68]=1>C(Cl)Cl>[CH3:65][S:66][C:67]1[CH:72]=[CH:71][C:70]([NH:73][C:28]([CH:9]2[CH:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=3[F:31])[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:26])([CH3:27])[CH3:25])[NH:10]2)=[O:30])=[CH:69][CH:68]=1
Reactant: CC(C)(C)CC1NC(C(=O)O)C(c2cccc(Cl)c2F)C1(C#N)c1ccc(Cl)cc1F
Reactant: CSc1ccc(N)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CSc1ccc(NC(=O)C2NC(CC(C)(C)C)C(C#N)(c3ccc(Cl)cc3F)C2c2cccc(Cl)c2F)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a stirred solution of rac (2R,3S,4R,5S)-3-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (250 mg, 0.44 mmol) in methylene chloride (10 mL), HATU (Aldrich, 332 mg, 0.88 mmol) was added followed by the addition of DIPEA (0.230 mL, 1.31 mmol) and 4-amino-phenyl methyl sulfide (Aldrich, 122 mg, 0.88 mmol). The mixture was stirred at rt for 2 hr. The reaction was quenched with addition of water. The mixture was extracted with methylene chloride (2×10 mL) and the extracts were dried with magnesium sulfate. The solvent was removed and the residue was purified on an ISCO machine (50 g column, eluent EtOAc/Hexanes, 5-10%) to give a white solid. 135 mg.
Reaction SMILES: CC(CC(C)(C)C)CC(O)=O.C1(CO)CCC(CO)CC1.[C:22]([O:34][CH3:35])(=[O:33])[C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=1>[Ru].O>[CH:26]1([C:27]([O:29][CH3:30])=[O:28])[CH2:25][CH2:24][CH:23]([C:22]([O:34][CH3:35])=[O:33])[CH2:32][CH2:31]1
Reactant: COC(=O)c1ccc(C(=O)OC)cc1
Agent: [Ru]
Agent: CC(CC(=O)O)CC(C)(C)C
Agent: OCC1CCC(CO)CC1
Solvent: O
Product: COC(=O)C1CCC(C(=O)OC)CC1

Procedure:
A 1 L four-necked flask equipped with a stirrer, a thermometer and a water-fractionating receiver with a cooling tube was charged with 483.5 g (3.06 mol) of 3,5,5-trimethylhexanoic acid, 216 g (1.5 mol) of 1,4-cyclohexane dimethanol (produced by hydrogenating a nucleus of dimethyl terephthalate in the presence of a ruthenium-supporting molded catalyst to obtain dimethyl 1,4-cyclohexanedicarboxylate, and then hydrogenating the thus obtained dimethyl 1,4-cyclohexanedicarboxylate in the presence of a copper-chromium molded catalyst), xylene (5% by weight on the basis of a total weight of the raw materials), and tin oxide as a catalyst (0.2% by weight on the basis of a total weight of the raw materials), and the contents of the flask were gradually heated to 220° C. under a nitrogen atmosphere. Then, the contents of the flask were subjected to esterification reaction under reduced pressure for about 8 h while removing water distilled off by the water-fractionating receiver until reaching a theoretical amount (72 g) thereof. After completion of the reaction, an excess amount of the acid was removed by distillation. Next, the resultant esterification reaction product was neutralized with an aqueous sodium hydroxide solution which was used in an excess amount relative to a total acid value of the esterification reaction product, and then washed with water until reaching a neutrality, thereby obtaining a crude esterification reaction product. Further, the thus obtained crude esterification reaction product was treated with activated carbon, and then filtered to obtain 568 g of 1,4-cyclohexane dimethanol di(3,5,5-trimethylhexanoate) (Compound 4). It was confirmed that the resultant ester had a total acid value of 0.01 mg KOH/g, an iodine number of less than 0.1 I2g/100 g and a molar ratio of cis-isomer to trans-isomer of 29/71. Various properties of the thus obtained compound 4 such as coefficient of traction, kinematic viscosity, viscosity index (VI), flash point and pour point thereof, are shown in Table 1.
Reaction SMILES: [CH3:1][CH:2](Br)[C:3]([C:5]1[CH:16]=[CH:15][C:8]([O:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])=[CH:7][CH:6]=1)=[O:4].[N:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[CH:20][CH:19]=1>C(#N)C>[N:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH2:25][CH2:26][N:27]([CH:2]([CH3:1])[C:3]([C:5]3[CH:16]=[CH:15][C:8]([O:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])=[CH:7][CH:6]=3)=[O:4])[CH2:28][CH2:29]2)=[CH:20][CH:19]=1
Reactant: COC(=O)COc1ccc(C(=O)C(C)Br)cc1
Reactant: c1cc(N2CCNCC2)ccn1
Solvent: CC#N
Product: COC(=O)COc1ccc(C(=O)C(C)N2CCN(c3ccncc3)CC2)cc1
Reaction time: 8 h

Procedure:
A solution of RS methyl 4-(2-methylbromoacetyl)phenoxyacetate (1.2 g) in acetonitrile (10 ml) was added dropwise over 30 minutes to a stirred solution of 1-(4-pyridyl)piperazine (1.3 g) in acetonitrile (30 ml) and the mixture stirred overnight. The mixture was then filtered and the filtrate evaporated to give an oil. Purification by flash chromatography, eluting first with dichloromethane then successively 2.5%, 3%, 4%, 5% and 10% v/v methanol/dichloromethane gave the title compound, 220 mg as a solid: m.p. 81°-83° C.; NMR (d6DMSO) δ 8.13(2H,d), 8.06(2H,d), 7.02(2H,d), 6.77(2H,d), 4.92(2H,s), 4.33(1H,q), 3.72(3H,s), 3.26(4H,t), 2.63(4H,t), 1.16(3H,d); m/e 384(M+H)+ ; calculated for C21H25N3O4 : C, 65.8; H, 6.6; N, 11.0. found C, 65.7; H, 6.8; N, 10.9%.
Reaction SMILES: O[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[O:10][CH3:11].C(N([CH2:17][CH3:18])CC)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>ClCCl>[CH3:11][O:10][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:2]=1[C:18]1[CH:17]=[CH:4][CH:3]=[CH:2][CH:9]=1)[CH:6]=[O:7]
Reactant: CCN(CC)CC
Reactant: COc1cc(C=O)ccc1O
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Product: COc1cc(C=O)ccc1-c1ccccc1
Temperature: 25 °C

Procedure:
To an ice-cold solution of 4-hydroxy-3-methoxy-benzaldehyde (1.00 g) in dichloromethane (22 mL) was added triethylamine (1.37 mL). Then trifluoromethanesulfonic anhydride (1.40 mL) was added dropwise, and the resulting mixture was stirred under ice-cooling for 45 minutes. Ice was added and the whole was partitioned between AcOEt (60 mL) and saturated aqueous sodium hydrogen carbonate (30 mL). The organic layer was washed successively with water/brine (3/1, 40 mL) and brine (30 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue (1.98 g) was dissolved in N,N-dimethylformamide (25 mL). Phenylboronic acid (0.882 g), sodium carbonate (1.39 g), water (5 mL) and tetrakis(triphenyl-phosphine)palladium(0) (0.380 g) were added, and the resulting mixture was stirred at 80° C. for 2.5 hours. The reaction mixture was cooled to room temperature and then partitioned between ethyl acetate (70 mL) and water (30 mL). The organic layer was washed with water/brine (1/1, 30 mL×2), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=10/1 to 5/1) to give the title compound (1.12 g).
Reaction SMILES: C([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[C@@H:10]([CH2:23][O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH2:9]1)C1C=CC=CC=1.C([O-])=O.[NH4+].CO>O.[Pd]>[Si:25]([O:24][CH2:23][C@@H:10]1[C@@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:21])([F:20])[F:22])[CH:14]=2)[CH2:12][NH:8][CH2:9]1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]
Reactant: CC(C)(C)[Si](C)(C)OC[C@H]1CN(Cc2ccccc2)C[C@@H]1c1cccc(C(F)(F)F)c1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: O
Solvent: CO
Product: CC(C)(C)[Si](C)(C)OC[C@H]1CNC[C@@H]1c1cccc(C(F)(F)F)c1
Temperature: 50 °C
Reaction time: 4 h
Yield: 101.8 %

Procedure:
At room temperature, 1.0 g of 10% palladium/carbon was added, while suspending in 10 ml of water, to a mixture of 9.69 g of (3R,4S)-1-benzyl-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-[3-(trifluoromethyl)phenyl]pyrrolidine, 5.70 mg of ammonium formate and 100 ml of methanol. This was vigorously stirred at 50° C. for 4 hours and then cooled down to room temperature, and the insoluble matter was removed by filtration through a celite layer. The filtrate was concentrated under a reduced pressure, and the thus obtained residue was purified by a silica gel column chromatography (chloroform-ethyl acetate) to obtain 7.89 g of (3R,4S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-[3-(trifluoromethyl)phenyl]pyrrolidine as a pale yellow oily substance.
Reaction SMILES: F[B-](F)(F)F.B(F)(F)[F:7].CCOCC.N[C:16]1[CH:17]=[CH:18][C:19]2[CH2:20][CH2:21][C@@H:22]3[C@@H:31]([C:32]=2[CH:33]=1)[CH2:30][CH2:29][C@@:27]1([CH3:28])[C@H:23]3[CH2:24][CH2:25][CH2:26]1.C(ON=O)(C)(C)C>C(Cl)Cl.CCCCC>[F:7][C:17]1[CH:16]=[CH:33][C:32]2[C@@H:31]3[C@H:22]([C@H:23]4[C@@:27]([CH2:29][CH2:30]3)([CH3:28])[CH2:26][CH2:25][CH2:24]4)[CH2:21][CH2:20][C:19]=2[CH:18]=1
Reactant: FB(F)F
Reactant: C[C@@]12CCC[C@H]1[C@@H]1CCc3ccc(N)cc3[C@H]1CC2
Agent: CC(C)(C)ON=O
Agent: F[B-](F)(F)F
Solvent: CCOCC
Solvent: CCCCC
Solvent: ClCCl
Product: C[C@@]12CCC[C@H]1[C@@H]1CCc3cc(F)ccc3[C@H]1CC2
Temperature: -15 °C
Reaction time: 0.25 h
Yield: 50 %

Procedure:
3-Fluoroestrone was synthesized from 2-aminoestrone by adapting the procedure reported by Doyle and Bryker (J. Org. Chem. 44, 1572-1574, 1979) for the synthesis of arenediaxonium tetrafluoroborate salts from aromatic amines. The procedure is as followed: To neat stirred boron trifluoride etherate (642 μL, 719 mg, 5.07 mmol) at −15° C. under Ar (g) was added a solution of 3-aminoestrone (101) (910 mg, 3.38 mmol) in dry CH2Cl2 (10 mL). After 15 min, a solution of t-butylnitrite (482 μL, 418 mg, 4.05 mmol) in dry CH2Cl2 (5 mL) was dropwise added. The now dark brown solution was stirred at −15° C. for 15 min, then at 0° C. for 30 min. Pentane was added to the solution and a gummy solid precipitated. The solvent was decanted and the residue was dried under vacuum to give a crude light brown solid. The neat solid was heated under vacuum at 70-80° C. in an oil bath for 15 min to give a crude orange solid. Purification by flash chromatography on SiO2 using 1:9 EtOAc/Hexanes gave 3-fluoroestrone (102) as a white solid (437 mg, 47%). M.p. 178° C.; [α]25D +152.0° (c 1.03, CDCl3); IR (ν) 3044, 3039, 2928, 1740 (CO), 1611, 1585, 1495, 1474, 1458, 1428, 1405, 1377, 1340, 1272, 1245, 1230, 1212, 1148, 1094, 1084, 1053, 1008, 908, 889, 817, 784, 718, 704, 642, 620, 580, 564, 467 cm−1; 1H NMR (CDCl3) δ 0.92 (3H, s), 1.37-1.70 (6H, m), 1.93-2.44 (6H, m), 2.52 (1H, dd, J=18.8 Hz, J′=9.0 Hz), 2.91 (2H, dd, J=8.4 Hz, J′=3.8 Hz), 6.82 (2H, dq, J=8.3 Hz, J′=2.8 Hz), 7.23 (1H, dd, J=8.5 Hz, J′=5.8 Hz); 13C NMR (CDCl3) δ 13.8, 21.6, 25.9, 26.3, 29.5, 31.5, 35.9, 38.1, 44.0, 47.9, 50.4, 112.5 (d, J=21.6 Hz), 115.1 (d, J=19.7 Hz), 126.8 (d, J=7.5 Hz), 135.3, 138.7, 161.0 (d, J=244.3 Hz), 220.7.
Reaction SMILES: [CH2:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[C:5]1=[O:14])[CH:2]=[CH2:3].[N+:15]([CH3:18])([O-:17])=[O:16]>O>[CH2:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([OH:13])([CH2:18][N+:15]([O-:17])=[O:16])[C:5]1=[O:14])[CH:2]=[CH2:3]
Reactant: C[N+](=O)[O-]
Reactant: C=CCN1C(=O)C(=O)c2ccccc21
Solvent: O
Product: C=CCN1C(=O)C(O)(C[N+](=O)[O-])c2ccccc21
Temperature: 40 °C
Reaction time: 24 h

Procedure:
1-allylindoline-2,3-dione (0.093 g) and nitromethane (0.15 ml) were added to water and the reaction mixture was vigorously stirred at a temperature of 40° C. for 24 hours. The obtained product was extracted with ethyl acetate and purified by silica gel column chromatography using ethyl acetate/hexane as eluents to afford pure product.