Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([OH:7])[CH2:2][CH2:3][CH:4]=[CH:5][CH3:6].[H-].[Na+].Cl[C:11]1[C:12]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[N:13][S:14][N:15]=1.O>O1CCCC1>[CH2:1]([O:7][C:11]1[C:12]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[N:13][S:14][N:15]=1)[CH2:2][CH2:3][CH:4]=[CH:5][CH3:6]
Reactant: CC=CCCCO
Reactant: Clc1nsnc1-c1cccnc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CC=CCCCOc1nsnc1-c1cccnc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 4-hexen-l-ol (900 mg, 9 mmol) and sodium hydride (310 mg, 9 mmol) in dry tetrahydrofuran was added a solution of 3-(4-chloro-1,2,5-thiadiazol-3-yl)pyridine (590 mg, 3 mmol) in dry tetrahydrofuran. The reaction mixture was stirred at room temperature for 1 h. Water was added and the mixture was extracted with ether. The ether phase was dried and evaporated to give the title compound.
Reaction SMILES: B.C(C[C:5]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])([C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22])[C@H:6]([C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[CH2:7][CH:8]([CH3:10])[CH3:9])=O.C(O)(=O)C[C:40](CC(O)=O)(C(O)=O)[OH:41]>O1CCCC1>[OH:41][CH2:40][C:5]([C:31]([O:33][C:34]([CH3:37])([CH3:35])[CH3:36])=[O:32])([C:21]([O:23][CH2:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)=[O:22])[C@H:6]([C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[CH2:7][CH:8]([CH3:10])[CH3:9]
Reactant: CC(C)C[C@@H](C(=O)OCc1ccccc1)C(CC=O)(C(=O)OCc1ccccc1)C(=O)OC(C)(C)C
Reactant: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: B
Solvent: C1CCOC1
Product: CC(C)C[C@@H](C(=O)OCc1ccccc1)C(CO)(C(=O)OCc1ccccc1)C(=O)OC(C)(C)C
Reaction time: 0.08 h

Procedure:
8.2 ml of a 1M solution of borane in tetrahydrofuran was added to a solution of 4.055 g of 1,2-dibenzyl 1-tert.butyl 1-(formylmethyl)-4-methyl-1,1,2(R)-pentanetricarboxylate in 40 ml of dry tetrahydrofuran. After stirring for 5 minutes, the mixture was acidified with 5% aqueous citric acid solution and was extracted twice with ethyl acetate. The combined extracts were washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate and evaporate. The residue was purified by flash chromatography on silica gel using hexane/ethyl acetate for the elution. There was obtained 2.518 g of 1,2-dibenzyl 1-tert.butyl 1-(hydroxymethyl)-4-methyl-1,1,2(R)-pentanetricarboxylate in the form of a colorless oil.
Reaction SMILES: C(N(CC)CC)C.[OH:8][CH:9]1[CH2:14][C:13]([CH3:16])([CH3:15])[NH+:12]([O-:17])[C:11]([CH3:19])([CH3:18])[CH2:10]1.[CH3:20][Si:21](Cl)([CH3:23])[CH3:22]>ClCCl>[CH3:20][Si:21]([CH3:23])([CH3:22])[O:8][CH:9]1[CH2:14][C:13]([CH3:15])([CH3:16])[NH+:12]([O-:17])[C:11]([CH3:19])([CH3:18])[CH2:10]1
Reactant: C[Si](C)(C)Cl
Reactant: CC1(C)CC(O)CC(C)(C)[NH+]1[O-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC1(C)CC(O[Si](C)(C)C)CC(C)(C)[NH+]1[O-]
Temperature: 25 °C
Yield: 98 %

Procedure:
To a solution in which 48.6 g (480 mmol) of triethylamine and 68.9 g (400 mmol) of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxide (TEMPOL) were dissolved in 100 mL of di-chloromethane, 47.8 g (440 mmol) of trimethylsilyl chloride was added at 0° C. The temperature was raised to 25° C. to carry out a reaction for 2 hours, and it was then concentrated by a rotary evaporator. To the residue 500 ml of water was added, and an extraction was carried out using 500 ml in total of ethyl acetate. The organic layer was concentrated by a rotary evaporator and the residue was dissolved in hexane and recrystallized to obtain 96.2 g of 4-trimethylsilyloxy-2,2,6,6-tetramethylpiperidine-N-oxide.
Reaction SMILES: [CH3:1][C:2]1[CH:13]=[C:6]2[C:7]([O:9][C:10](=[O:12])[NH:11][C:5]2=[CH:4][CH:3]=1)=[O:8].[C:14](=O)([O-])[O-].[Na+].[Na+].IC>CN(C)C=O>[CH3:14][N:11]1[C:10](=[O:12])[O:9][C:7](=[O:8])[C:6]2=[CH:13][C:2]([CH3:1])=[CH:3][CH:4]=[C:5]12
Reactant: O=C([O-])[O-]
Reactant: Cc1ccc2[nH]c(=O)oc(=O)c2c1
Agent: [Na+]
Solvent: CI
Solvent: CN(C)C=O
Product: Cc1ccc2c(c1)c(=O)oc(=O)n2C
Temperature: 0 °C

Procedure:
A solution of 26.6 g of 5-methylisatoic anhydride in 150 ml of dimethylformamide is treated with 17.5 g of anhydrous sodium carbonate, then with 32 g of iodomethane, and the mixture is stirred at 20°-25° C. for 18 hrs. The reaction mixture is poured into 1.25 liter of ice water and the resulting precipitate of N,5-dimethylisatoic anhydride is collected by filtration, washed with water and dried; mp 166°-169° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:13][CH2:14][S:15][S:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:9][C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:22][C:23]#[N:24].CCN(C(C)C)C(C)C.[Cl-].[NH4+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]([CH2:13][CH2:14][S:15][S:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:9][C:10]([O:12][CH2:22][C:23]#[N:24])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: N#CCBr
Reactant: CC(C)(C)OC(=O)N(CCSSC(C)(C)C)CC(=O)O
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N(CCSSC(C)(C)C)CC(=O)OCC#N
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 95.6 %

Procedure:
2-((tert-Butoxycarbonyl)(2-(tert-butyldisulfanyl)ethyl)amino)acetic acid (Compound 6f-A, 268.1 mg, 0.83 mmol) and 2-bromoacetonitrile (199 mg, 1.66 mmol) were dissolved in DMF (1.0 ml), DIPEA (0.43 ml, 2.49 mmol) was added and the mixture was stirred at room temperature for 15 minutes. A saturated aqueous ammonium chloride solution was added to the reaction solution, followed by extraction with diethyl ether. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane:ethyl acetate=3:1) to afford the title compound (287.7 mg, 96%).
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@H:7]([CH2:9][OH:10])[OH:8])[OH:6])[OH:4].O=C[C@@H]([C@H]([C@H]([C@@H](CO)O)O)O)O>>[O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([CH2:9][OH:10])[OH:8])[OH:6])[OH:4]
Reactant: O=C[C@H](O)[C@@H](O)[C@@H](O)CO
Agent: O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO
Product: O=C[C@H](O)[C@@H](O)[C@H](O)CO

Procedure:
In a preferred embodiment, the mixture fed onto the SMB comprises from about 5 wt. % to about 85 wt. %; of a mixture of D-xylose and L-arabinose. Still further, the at least two components fed onto the SMB comprise D-xylose and L-arabinose. Still further, after the separation step L-arabinose is present in one eluent fraction at from about 85 wt. % to about 100 wt. %. Still further preferably, minor components, eg., galactose, are allowed to go into the D-xylose fraction, thereby providing an L-arabinose fraction comprised from about 85 wt % to about 100 wt % L-arabinose. In a separate embodiment, minor components, eg., galactose, are allowed to go with the L-arabinose fraction, thereby providing a D-xylose fraction comprised from about 85 wt. % to about 100 wt. % D-xylose. Still further, it is preferred that the D-xylose fraction is comprised of from about 85 wt. % to about 100 wt. % D-xylose. Those skilled in the art will recognize that these fractions can be additionally purified by crystallization.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[N:14]2[N:15]=[CH:16][C:17]([S:18](=[O:25])(=[O:24])[NH:19][CH2:20][CH2:21][O:22][CH3:23])=[C:13]2[N:12]=[CH:11][C:10]=1[C:26]([O:28]CC)=O.[F:31][C:32]1[CH:37]=[CH:36][C:35]([CH:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)=[CH:34][CH:33]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[N:14]2[N:15]=[CH:16][C:17]([S:18]([NH:19][CH2:20][CH2:21][O:22][CH3:23])(=[O:24])=[O:25])=[C:13]2[N:12]=[CH:11][C:10]=1[C:26]([N:41]1[CH2:42][CH2:43][CH:38]([C:35]2[CH:34]=[CH:33][C:32]([F:31])=[CH:37][CH:36]=2)[CH2:39][CH2:40]1)=[O:28]
Reactant: CCOC(=O)c1cnc2c(S(=O)(=O)NCCOC)cnn2c1Nc1ccccc1Cl
Reactant: Fc1ccc(C2CCNCC2)cc1
Product: COCCNS(=O)(=O)c1cnn2c(Nc3ccccc3Cl)c(C(=O)N3CCC(c4ccc(F)cc4)CC3)cnc12
Yield: 16.6 %

Procedure:
Using ethyl 7-(2-chlorophenylamino)-3-[N-(2-methoxyethyl)sulfamoyl]pyrazolo[1,5-a]pyrimidine-6-carboxylate (0.459 g, 1.008 mmol) obtained in step 1 and 4-(4-fluorophenyl)piperidine (0.158 g, 0.881 mmol) instead of 4-phenylpiperidine, and in the same manner as in Example 1 step 4, the title compound (0.086 g, 15%) was obtained.
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[CH2:7][CH:8]([CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1)[C:9]([OH:11])=O)([CH3:4])([CH3:3])[CH3:2].[N:23]1(C(N)=O)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>>[C:1]([O:5][C:6](=[O:22])[CH2:7][CH:8]([C:9]([N:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)=[O:11])[CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: NC(=O)N1CCCCC1
Reactant: CC(C)(C)OC(=O)CC(CCCc1ccc(Cl)cc1)C(=O)O
Product: CC(C)(C)OC(=O)CC(CCCc1ccc(Cl)cc1)C(=O)N1CCCCC1

Procedure:
2[[3-(4-Chlorophenyl)-propyl]-succinic acid 4-tert-butyl ester (WO 95/04033) (5 g, 15.3 mmol) was converted to the corresponding piperidine amide by the method described previously (Example 1, Step G). Yield 4.01 g (67%). 1H-NMR: δ (CDCl3), 7.23 (2H, d, J=8.3 Hz), 7.08 (2H, d, J=8.3 Hz), 3.68-3.42 (4H, m), 3.12 (1H, m), 2.69 (1H, dd, J=8.4, 16.4 Hz), 2.62-2.49 (2H, m), 2.29 (1H, dd, J=5.6, 16.4 Hz), 1.72-1.33 (10H, m) and 1.41 (9H, s).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[N:11]1[CH2:14][CH:13]([OH:15])[CH2:12]1.[H-].[Na+].Cl[C:19]1[N:20]=[N:21][C:22](Cl)=[CH:23][C:24]=1[N:25]1[CH2:30][CH2:29][CH:28]([C:31](=[O:33])[CH3:32])[CH2:27][CH2:26]1>CN(C=O)C.O>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[N:11]1[CH2:12][CH:13]([O:15][C:19]2[N:20]=[N:21][CH:22]=[CH:23][C:24]=2[N:25]2[CH2:30][CH2:29][CH:28]([CH:31]([OH:33])[CH3:32])[CH2:27][CH2:26]2)[CH2:14]1
Reactant: OC1CN(c2ccc3ccccc3n2)C1
Reactant: CC(=O)C1CCN(c2cc(Cl)nnc2Cl)CC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(O)C1CCN(c2ccnnc2OC2CN(c3ccc4ccccc4n3)C2)CC1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 68.4 %

Procedure:
To a solution of 1-(quinolin-2-yl)azetidin-3-ol (see PREPARATION P1.2, step 1; 0.78 g, 3.8 mmol) in DMF (20 mL) at room temperature was added sodium hydride (60% wt in mineral oil) (0.18 g, 7.6 mmol). The mixture was stirred at room temperature for 10 min and then 1-(1-(3,6-dichloropyridazin-4-yl)piperidin-4-yl)ethanone (1.0 g, 3.8 mmol) was added. The reaction mixture was stirred at room temperature for 1 hour and then diluted with water (20 mL) and extracted with EtOAc (2×30 mL). The combined organic extracts were washed with water (10 mL) and brine (10 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (5% to 30% EtOAc in hexanes) to give the title product (1.1 g, 2.6 mmol, 70% yield) as white solid. ESI-MS (M+1): 438 calc. for C24H25ClN4O2 437.
Reaction SMILES: S(Cl)([Cl:4])(=O)=O.[CH3:6][O:7][C:8]1[CH:9]=[CH:10][C:11]2[S:15][C:14](S)=[N:13][C:12]=2[CH:17]=1>C1COCC1.CCOC(C)=O>[Cl:4][C:14]1[S:15][C:11]2[CH:10]=[CH:9][C:8]([O:7][CH3:6])=[CH:17][C:12]=2[N:13]=1
Reactant: O=S(=O)(Cl)Cl
Reactant: COc1ccc2sc(S)nc2c1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COc1ccc2sc(Cl)nc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 20 %

Procedure:
Sulfuryl chloride (1.64 mL) was added to a solution of 5-methoxy-2-mercaptobenzothiazole in THF (20 mL). After stirring overnight, ice water was added. The reaction mixture was allowed to warm to rt and was diluted with EtOAc (100 mL). This was washed with water (50 mL) and brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was purified by column chromatography (0 to 3% EtOAc in hexanes gradient), yielding 0.407 g (20%) of the title compound as a white solid. LC-MS: RT=9.05 min., [M+H]+=200.0. Rf=0.38 in 10% EtOAc/Hexanes.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:6][CH:7]=1.C1C(=O)N([Br:21])C(=O)C1.N(C(C)(CC(C)C)C#N)=NC(C)(CC(C)C)C#N>ClCCCl>[Br:21][CH2:1][C:2]1[N:3]=[N:4][C:5]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:6][CH:7]=1
Reactant: Cc1ccc(-c2ccccc2)nn1
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)CC(C)(C#N)N=NC(C)(C#N)CC(C)C
Solvent: ClCCCl
Product: BrCc1ccc(-c2ccccc2)nn1
Temperature: 80 °C
Reaction time: 1 h
Yield: 33.2 %

Procedure:
To a solution of 3-methyl-6-phenylpyridazine (925 mg, 5.43 mmol) in 1,2-dichloroethane (28 ml) were added NBS (1.07 g, 6.01 mmol) and 2,2′-azobis(2,4-dimethylvaleronitrile) (67.3 mg, 0.271 mmol), followed by stirring at 80° C. for 1 hour. During the reaction, 2,2′-azobis(2,4-dimethylvaleronitrile)(134 mg, 0.540 mmol) was additionally added in two portions. After completion of the reaction, the reaction solution was concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography (eluent; hexane:ethyl acetate=5:1→0:1 (V/V)), and fractions containing the desired compound were concentrated under reduced pressure to afford the title compound (449 mg) as a slightly brown solid. (Yield: 33%)
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:14])=[CH:4][CH:5]=[C:6]2[NH:12][C:11](=[O:13])[O:10][C:8](=O)[C:7]=12.[NH:15]1[CH2:22][CH2:21][CH2:20][C@H:16]1C(O)=O.O>CN(C)C=O>[Cl:1][C:2]1[C:7]2[C:8](=[O:10])[N:15]3[CH2:22][CH2:21][CH2:20][C@H:16]3[C:11](=[O:13])[NH:12][C:6]=2[CH:5]=[CH:4][C:3]=1[F:14]
Reactant: O=C(O)[C@@H]1CCCN1
Reactant: O=c1[nH]c2ccc(F)c(Cl)c2c(=O)o1
Solvent: CN(C)C=O
Solvent: O
Product: O=C1Nc2ccc(F)c(Cl)c2C(=O)N2CCC[C@@H]12

Procedure:
3.3 g (0.015 mol) of 6-chloro-5-fluoroisatoic acid anhydride and 2 g (0.017 mol) of L-proline in 7.5 ml of dimethylformamide are heated to 120° for 2 hours, cooled, treated with 12 ml of distilled water and the precipitated brown crystals are filtered off. By recrystallization of the crude product from acetone/hexane there is obtained (S)-6-chloro-7-fluoro-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H)-dione of melting point 217°-219°.
Reaction SMILES: [CH2:1]([SH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:15][O:16][C:17](=[O:29])[C:18]1[CH:23]=[C:22]([Br:24])[CH:21]=[C:20]([N+:25]([O-:27])=[O:26])[C:19]=1Cl>CO.O>[CH3:15][O:16][C:17](=[O:29])[C:18]1[CH:23]=[C:22]([Br:24])[CH:21]=[C:20]([N+:25]([O-:27])=[O:26])[C:19]=1[S:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: SCc1ccccc1
Reactant: COC(=O)c1cc(Br)cc([N+](=O)[O-])c1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CO
Product: COC(=O)c1cc(Br)cc([N+](=O)[O-])c1SCc1ccccc1
Temperature: 20 °C
Reaction time: 2 h
Yield: 93.8 %

Procedure:
71.6 g (0.58 mol) of benzyl mercaptan are dissolved in 2.9 l of methanol/water (8:2), and 79.8 g (0.58 mol) of potassium carbonate are added. At 0°-5° C., 170 g (0.58 mol) of 5-bromo-2-chloro-3-nitrobenzoic acid methyl ester are added in portions over a period of 2.5 hours with stirring. Stirring is then continued for a further 2 hours and the internal temperature is then raised to 20° C. The resulting precipitate is then isolated by filtration, washed with a small amount of water and subsequently with 500 ml of methanol/water. After drying, 208 g (94%) of pale yellow product are obtained. Recrystallisation from 400 ml of methanol gives 190 g (86% of the theoretical yield) of product having a melting point of 65°-66° C.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.[H-].[Na+].[CH2:13]([O:15][CH:16]([O:19][CH2:20][CH3:21])[CH2:17]Br)[CH3:14].O>CN(C=O)C>[CH2:13]([O:15][CH:16]([O:19][CH2:20][CH3:21])[CH2:17][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1)[CH3:14]
Reactant: CCOC(CBr)OCC
Reactant: CC(=O)c1ccc(O)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(COc1ccc(C(C)=O)cc1)OCC
Temperature: 120 °C
Reaction time: 8 h
Yield: 133.4 %

Procedure:
To a solution of 1-(4-hydroxyphenyl)ethanone (1.00 g, 7.34 mmol) in N,N′-dimethylformamide (24 mL), sodium hydride (purity 50%) (380 mg, 8.07 mmol), and bromoacetaldehyde diethyl acetal (1.30 mL, 8.81 mmol) were added under ice-cold conditions and stirred at 120° C. overnight. Under ice-cold conditions, the reaction solution was added water, and extracted with diethylether. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The obtained residue was purified by silica-gel column chromatography (hexane/ethyl acetate), and the title compound (2.47 g (yield >100%)) was obtained as a yellow oil.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[O:8])=[CH:5][N:4]=1.C(N(CC)CC)C.[N+:20]([CH3:23])([O-:22])=[O:21]>>[N+:20]([CH2:23][CH:7]([C:6]1[CH:5]=[N:4][C:3]([C:2]([F:1])([F:11])[F:12])=[CH:10][CH:9]=1)[OH:8])([O-:22])=[O:21]
Reactant: O=Cc1ccc(C(F)(F)F)nc1
Reactant: C[N+](=O)[O-]
Solvent: CCN(CC)CC
Product: O=[N+]([O-])CC(O)c1ccc(C(F)(F)F)nc1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
In a 100 mL round-bottomed flask, 6-(trifluoromethyl)nicotinaldehyde (2.61 g, 14.9 mmol) was combined with nitromethane (20 ml) to give a light yellow solution. triethylamine (1.51 g, 2.08 ml, 14.9 mmol) was added. The reaction mixture was stirred at room temperature for 1.5 h and concentrated in vacuo. The resultant residue was purified by flash chromatography (silica gel, 80 g, 0.2% to 1.2% MeOH in dichloromethane gradient) to afford 2-nitro-1-(6-(trifluoromethyl)pyridin-3-yl)ethanol (2.4 g) as an off-white solid.
Reaction SMILES: Cl.Cl.[NH2:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][CH:8]([N:14]([CH2:18][CH2:19][CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:15][CH2:16][CH3:17])[CH2:9]2.C(N(CC)CC)C.[C:35](Cl)(=[O:37])[CH3:36]>C(Cl)Cl>[C:35]([NH:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][CH:8]([N:14]([CH2:18][CH2:19][CH2:20][CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[CH2:15][CH2:16][CH3:17])[CH2:9]2)(=[O:37])[CH3:36]
Reactant: CCCN(CCCCc1ccccc1)C1CCc2c(N)cccc2C1
Reactant: CC(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCN(CCCCc1ccccc1)C1CCc2c(cccc2NC(C)=O)C1
Reaction time: 3 h

Procedure:
0.90 g (0.0022 mol) of 5-amino-2-[N-(4-phenylbutyl)-N-n-propyl-amino]-tetraline-dihydrochloride (Example 4.5.4) and 1.00 g (0.0099 mol) of triethylamine are mixed with 15 ml of absolute methylene chloride with stirring and cooling with ice and 0.20 g (2.55 mmol) of acetylchloride in 5 ml of absolute methylene chloride are added. After 3 hours at ambient temperature or 30 minutes refluxing, the mixture is extracted three times with 5 ml of water, dried with sodium sulphate and concentrated by rotary evaporation, finally at 80° C. under a complete water-jet vacuum. The residue is crystallised from diethylether/petroleum ether.
Reaction SMILES: [OH:1][C:2]1[C:19]([CH:20]=[O:21])=[CH:18][C:17]2[C@@H:16]3[C@H:7]([C@H:8]4[C@@:12]([CH2:14][CH2:15]3)([CH3:13])[C:11](=[CH2:22])[CH2:10][CH2:9]4)[CH2:6][CH2:5][C:4]=2[CH:3]=1.[H][H]>CCOC(C)=O.[Pd]>[OH:1][C:2]1[C:19]([CH:20]=[O:21])=[CH:18][C:17]2[C@@H:16]3[C@H:7]([C@H:8]4[C@@:12]([CH2:14][CH2:15]3)([CH3:13])[C@@H:11]([CH3:22])[CH2:10][CH2:9]4)[CH2:6][CH2:5][C:4]=2[CH:3]=1
Reactant: C=C1CC[C@H]2[C@@H]3CCc4cc(O)c(C=O)cc4[C@H]3CC[C@]12C
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: C[C@H]1CC[C@H]2[C@@H]3CCc4cc(O)c(C=O)cc4[C@H]3CC[C@]12C
Yield: 76.2 %

Procedure:
To a solution of 3-hydroxy-17-methyleneestra-1,3,5(10)-triene-2-carboxaldehyde (23, 0.401 g, 1.35 mmol) in EtOAc (10 mL) was added 10 palladium on carbon (0.060 g). The reaction mixture was stirred for 4 h under the hydrogen atmosphere at room temperature. After the catalyst was filtered, the solvent was evaporated at reduced pressure. The residue was purified by column chromatography (silica gel) using n-hexane:EtOAc (10:1→2:1, v/v) to afford 0.307 g of 27 (76% yield).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([O:21][CH3:22])[C:18]=1[O:19][CH3:20])[CH:5]=[C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:8][C:7]1=[O:15].C(=O)([O-])[O-].[Na+].[Na+].[CH:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=[CH:31][C:30]=1B(O)O>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:20][O:19][C:18]1[C:17]([O:21][CH3:22])=[CH:16][C:4]([CH:5]=[C:6]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]2=[O:15])=[C:3]([C:31]2[CH:30]=[CH:29][C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH:32]=2)[CH:2]=1
Reactant: OB(O)c1ccc2ccccc2c1
Reactant: COc1cc(C=C2C(=O)Nc3ccccc32)cc(Br)c1OC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: COc1cc(C=C2C(=O)Nc3ccccc32)c(-c2ccc3ccccc3c2)cc1OC
Reaction time: 12 h
Yield: 30.9 %

Procedure:
Tetrakis(triphenylphosphine)palladium (0) (0.02 g) was added to a solution of 3-(3-bromo-4,5-dimethoxybenzylidene)-1,3-dihydroindol-2-one (0.20 g) in toluene (1 ml) and ethanol (1 ml) followed by addition of 2M aqueous sodium carbonate (1.1 ml). To this mixture was added naphthalene-2-boronic acid (0.11 g), and the mixture was held at 100° C. in a sealed tube for 12 hours. The precipitate which formed was filtered, washed with ethanol and then dissolved in 20% methanol/toluene, filtered and concentrated. The resulting solid was triturated with hexanes and dried to afford 0.07 g (29%) of 3-(4,5-dimethoxy-2-naphthalen-2-ylbenzylidene)-1,3-dihydroindol-2-one as an orange solid.
Reaction SMILES: C[O:2][C:3](=O)[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]#[N:12])=[C:7]([O:13][CH3:14])[C:6]=1[Cl:15].[BH4-].[Li+]>C1COCC1.CCOCC>[Cl:15][C:6]1[C:7]([O:13][CH3:14])=[C:8]([C:11]#[N:12])[CH:9]=[CH:10][C:5]=1[CH2:4][CH2:3][OH:2]
Reactant: COC(=O)Cc1ccc(C#N)c(OC)c1Cl
Agent: [BH4-]
Agent: [Li+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: COc1c(C#N)ccc(CCO)c1Cl
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of methyl(2-chloro-4-cyano-3-methoxyphenyl)acetate (700 mg, 2.92 mmol) in THF (30 mL) was added 2M lithium borohydride (1.46 mL, 2.92 mmol) and the reaction was stirred at RT for 16 hours. The reaction was diluted with ether and quenched into water containing 2N HCl. The mixture was extracted twice with ethyl acetate and the organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The product mixture was separated by flash chromatography (10-40% ethyl acetate/hexanes) to afford the title product. 1H-NMR (400 MHz, CDCl3) δ ppm 3.10 (t, J=6.4 Hz, 2H), 3.94 (t, J=6.4 Hz, 2H), 4.08 (s, 3H), 7.175 (d, J=7.8 Hz, 1H), 7.46 (d, J=7.8 Hz, 1H).
Reaction SMILES: [O:1]1[CH2:5][CH2:4][CH:3]([CH2:6][N:7]2[CH2:12][CH2:11][C:10](=O)[CH2:9][CH2:8]2)[CH2:2]1.Cl.[NH2:15][OH:16]>>[O:1]1[CH2:5][CH2:4][CH:3]([CH2:6][N:7]2[CH2:12][CH2:11][C:10](=[N:15][OH:16])[CH2:9][CH2:8]2)[CH2:2]1
Reactant: O=C1CCN(CC2CCOC2)CC1
Reactant: NO
Agent: Cl
Product: ON=C1CCN(CC2CCOC2)CC1

Procedure:
1-(3-Tetrahydrofuranylmethyl)-4-piperidone oxime is prepared from 1-(3-tetrahydrofuranylmethyl)-4-piperidone and hydroxylamine hydrochloride essentially as described above in Example 38, Scheme C, step b.