Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH3:17])[CH:6]=[CH:5][C:4]([S:7]([NH:10][C@@H:11]([CH2:14][CH2:15][OH:16])[CH2:12]O)(=[O:9])=[O:8])=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH3:25][S:26](Cl)(=[O:28])=[O:27].O>C(Cl)Cl>[CH3:25][S:26]([O:16][CH2:15][CH2:14][CH:11]1[CH2:12][N@@:10]1[S:7]([C:4]1[CH:5]=[CH:6][C:1]([CH3:17])=[CH:2][CH:3]=1)(=[O:9])=[O:8])(=[O:28])=[O:27]
Reactant: Cc1ccc(S(=O)(=O)N[C@H](CO)CCO)cc1
Reactant: CS(=O)(=O)Cl
Agent: Cc1ccc(S(=O)(=O)[N@@]2CC2CCOS(C)(=O)=O)cc1
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)[N@]2CC2CCOS(C)(=O)=O)cc1
Temperature: -5 °C
Reaction time: 0.5 h

Procedure:
(S)-2-(p-Toluenesulfonylamino)-1,4-butanediol, 2, (46 g) was dissolved in methylene chloride (450 mL) and triethylamine (60 g) was added. The resulting solution was cooled to -5° C. under a nitrogen atmosphere and a solution of methanesulfonyl chloride (42.0 g) in methylene chloride (110 mL) was added dropwise over 3 hours. The resulting mixture was stirred an additional 0.5 hour at 0° to -5° C. and water (150 mL) and methylene chloride (350 mL) were cautiously added. The layers were separated and the organic layer extracted with 0.1N HCl (100 mL) and demineralized water (100 mL) and then concentrated under vacuum to give (S)-2-(2'-methanesulfonyloxyethyl)-1-(p-toluenesulfonyl)aziridine, 3, as a light yellow solid (57.2 g) which was used directly in the next step without further purification. A portion was recrystallized from ethyl acetate and hexanes: mp 78°-80° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=O)[CH:16]([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[CH2:17][CH2:18][C:19]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:38]O>CO>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:16]([C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)=[CH:17][CH:18]=[C:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[N:38]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NO
Reactant: COc1ccc(C(CCC(=O)c2ccc(F)cc2)C(=O)c2ccc(OCc3ccccc3)cc2)cc1
Agent: Cl
Solvent: CO
Product: COc1ccc(-c2ccc(-c3ccc(F)cc3)nc2-c2ccc(OCc3ccccc3)cc2)cc1
Yield: 40.6 %

Procedure:
The 1-(4-benzyloxyphenyl)-2-(4-methoxyphenyl)-5-(4-fluorophenyl)pentan-1,5-dione (1.0 g, 2.4 mmol) and hydroxylamine hydrochloride (0.2 g, 2.9 mmol) were refluxed in 30 mL of MeOH for 48 h, worked up, and purified to give 0.45 g (40 % yield) of product: mp 114°-115° C.; 1H NMR (CDCl3) d 3.82 (s, 3H, OCH3), 5.06 (s, 2H, OCH2Ar), 6.83-6.89 (m, 4H, ArH), 7.13-7.19 (m, 4H, ArH), 7.34-7.44 (m, 7H, ArH), 7.65-7.74 (dd, 2H, J=8, ArH), 8.10-8.14 (m, 2H, ArH); MS(FD) 461(M+). Anal. Calcd for C31H24NO2F: C, 80.67; H, 5.24; N,3.03. Found: C, 80.87; H, 5.30; N, 3.09.
Reaction SMILES: [Si]([O:8][C@@H:9]1[CH2:22][C@@H:12]2[O:13][C:14](=[O:21])[CH2:15][CH2:16][CH2:17][CH:18]=[CH:19][CH2:20][C@@H:11]2[C@H:10]1/[CH:23]=[CH:24]/[C@@H:25]([O:38][Si](CC)(CC)CC)[CH2:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:37])([F:36])[F:35])[CH:29]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>>[OH:8][C@@H:9]1[CH2:22][C@@H:12]2[O:13][C:14](=[O:21])[CH2:15][CH2:16][CH2:17][CH:18]=[CH:19][CH2:20][C@@H:11]2[C@H:10]1/[CH:23]=[CH:24]/[C@@H:25]([OH:38])[CH2:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:37])([F:35])[F:36])[CH:29]=1
Reactant: CC[Si](CC)(CC)O[C@H](/C=C/[C@@H]1[C@H]2CC=CCCCC(=O)O[C@H]2C[C@H]1O[Si](C)(C)C(C)(C)C)COc1cccc(C(F)(F)F)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: CC[Si](CC)(CC)O[C@H](/C=C/[C@@H]1[C@H]2C/C=C\CCCC(=O)O[C@H]2C[C@H]1O[Si](C)(C)C(C)(C)C)COc1cccc(C(F)(F)F)c1
Agent: O=C1CCC/C=C\C[C@@H]2[C@@H](/C=C/[C@@H](O)COc3cccc(C(F)(F)F)c3)[C@H](O)C[C@@H]2O1
Product: O=C1CCCC=CC[C@@H]2[C@@H](/C=C/[C@@H](O)COc3cccc(C(F)(F)F)c3)[C@H](O)C[C@@H]2O1
Reaction time: 2 h

Procedure:
(8aR,9R,10R,11 aS,Z)-10-(tert-butyldimethylsilyloxy)-9-((R,E)-3-(triethylsilyloxy)-4-(3-(trifluoromethyl)phenoxy)but-1-enyl)-4,5,8,8a,9,10,11,11a-octahydrocyclopenta[b]oxecin-2(3H)-one (20 mg, 0.003 mmol) and 1 ml TBAF (1M in tetrahydrofuran) was added into 10 ml round-bottom flask. The reaction mixture was stirred for 2 hours and quenched by 1 ml saturated NaHCO3 aqueous solution. Then, the mixture was phase separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and dried over anhydrous MgSO4. The solid was filtered off and organic solvent was evaporated off under vacuum. The crude product was purified by chromatography and then concentrated under reduced pressure to provide 10 mg of the title compound as an oil. (80% yield).
Reaction SMILES: [Na].[C:2]([NH:5][OH:6])([NH2:4])=[NH:3].OS(O)(=O)=O.CO[C:14](=O)[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]>C(O)C>[NH2:3][C:2]1[N:4]=[C:27]([CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH3:14])[O:6][N:5]=1
Reactant: N=C(N)NO
Reactant: CCCCCCCCCCCCCC(=O)OC
Agent: O=S(=O)(O)O
Agent: [Na]
Solvent: CCO
Product: CCCCCCCCCCCCCc1nc(N)no1
Reaction time: 0.25 h

Procedure:
Sodium metal (1.6 g, 0.068 mol) was added to 4 Å molecular sieves (12 g) and ethanol (200 mL) under nitrogen. The mixture was stirred for 15 minutes, then hydroxyguanidine sulfate (9.32 g, 0.035 mol) added and the mixture stirred for 30 minutes. Methyltetradecanoate (1.43 g, 0.006 mol) was then added and the mixture refluxed for 1.5 hours, allowed to cool, filtered, and concentrated. The concentrate was partitioned between CH2Cl2 and water. The organic layer was washed with water and brine, dried with Na2SO4, filtered, concentrated, and triturated with hexane. The resulting solid was filtered, washed with hexane, and dried in vacuo to yield 0.23 g, m.p. 90°-91° C.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:5]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:4][N:3]=1.[NH2:18][NH2:19]>C1COCC1>[NH:18]([C:2]1[N:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:5]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:4][N:3]=1)[NH2:19]
Reactant: CCOC(=O)c1cnc(Cl)nc1C(=O)OCC
Reactant: NN
Solvent: C1CCOC1
Product: CCOC(=O)c1cnc(NN)nc1C(=O)OCC
Yield: 96 %

Procedure:
The title compound was prepared as described in Example 18, but employing a solution of diethyl 2-chloropyrimidine-4,5-dicarboxylate (0.21 g, 0.83 mmol) and hydrazine (0.13 g, 4.2 mmol) in THF (10 mL) resulting in 96% yield (0.20 g); 1H NMR (CDCl3) δ 8.93 (bs, 1H), 8.34 (bs, 1H), 4.40 (m, 4H), 4.18 (bs, 2H), 1.35 (m, 6H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1.C(Cl)(=O)C(Cl)=O.C(=O)([O-])[O-].[K+].[K+].[CH:29]([NH:32][CH:33]([CH3:35])[CH3:34])([CH3:31])[CH3:30]>C(Cl)Cl.CN(C=O)C>[CH:29]([N:32]([CH:33]([CH3:35])[CH3:34])[C:12](=[O:14])[C:11]1[CH:10]=[CH:9][C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[CH3:1])=[CH:16][CH:15]=1)([CH3:31])[CH3:30]
Reactant: Cc1ccccc1-c1ccc(C(=O)O)cc1
Reactant: CC(C)NC(C)C
Agent: O=C(Cl)C(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: Cc1ccccc1-c1ccc(C(=O)N(C(C)C)C(C)C)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a suspension of 4-(2-methylphenyl)benzoic acid (4.00 g, 18.8 mmol) in DCM (150 mL) was added oxalyl chloride (10.00 g, 78.8 mmol) followed by 5 drops of DMF. The reaction mixture was stirred at RT for 3 h until a clear solution resulted. The solvent was removed in vacuo. The residue was dissolved with DCM (100 mL) and treated with aq. potassium carbonate (3.41 mL, 56.5 mmol). The reaction mixture was cooled to 0° C., and a solution of diisopropylamine (5.33 mL, 37.7 mmol) in DCM (50 mL) was added dropwise. The resulting mixture was stirred at RT over 12 h. The resulting mixture was quenched by the slow addition of saturated aqueous Na2CO3 (100 mL). The organic phase was separated and aqueous phase was extracted with dichloromethane (3×60 mL). The combined organic phases were washed with brine. The resulting organic solution was then dried over magnesium sulfate and concentrated under reduced pressure to give N,N-diisopropyl 4-(2-methylphenyl)benzamide as an off-white solid. MS (ESI, pos.ion) m/z: 296 (M+1)
Reaction SMILES: C([N:11]1[CH2:34][CH2:33][N:14]2[C:15]3[C:20]([NH:21][C:22](=[O:23])[CH:13]2[CH2:12]1)=[CH:19][C:18]([C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:25]=1[CH3:32])=[CH:17][CH:16]=3)(OCC1C=CC=CC=1)=O.C1CCCCC=1>C(O)C.[Pd]>[CH3:31][O:30][C:27]1[CH:28]=[CH:29][C:24]([C:18]2[CH:19]=[C:20]3[C:15](=[CH:16][CH:17]=2)[N:14]2[CH2:33][CH2:34][NH:11][CH2:12][CH:13]2[C:22](=[O:23])[NH:21]3)=[C:25]([CH3:32])[CH:26]=1
Reactant: COc1ccc(-c2ccc3c(c2)NC(=O)C2CN(C(=O)OCc4ccccc4)CCN32)c(C)c1
Agent: [Pd]
Solvent: C1=CCCCC1
Solvent: CCO
Product: COc1ccc(-c2ccc3c(c2)NC(=O)C2CNCCN32)c(C)c1
Temperature: 25 °C
Reaction time: 5 h
Yield: 24.4 %

Procedure:
Deprotection procedure: To a solution of 3-carbobenzyloxy-8-(4-methoxy-2-methylpheny)-2,3,4, 4a-tetrahydro-1H-pyrazino [1,2-a]quinoxalin-5(6H) -one (0.38 mmol) in 6 ml absolute ethanol was added 10% Pd/C (150 mg) and excess cyclohexene (3 ml). The black reaction mixture was heated to reflux. After 5 h, the mixture was cooled to rt and filtered through a pad of celite, washing heavily with methanol. The filtrate was concentrated to a colorless residue. The crude material was purified by radial PLC (1 mm plate, load and elute with methanol) to give the title compound as a colorless oil (30 mg, 24%). 1H NMR (CDCl3, 300 MHz) δ7.12 (d, J=8.1 Hz, 1H), 6.95 (dd, J=8.5, 1.9 Hz, 1H), 6.76-6.82 (m, 3H), 6.67 (d, J=1.8 Hz, 1H), 3.83 (s, 3H), 3.53-3.67 (m, 3H), 3.18 (m, 1H), 2.79-3.01 (m, 3H), 2.26 (s, 3H) ppm. MS (ESI) m/z=324.2 [M+H]+.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH2:7]Cl)([O-:3])=[O:2].[CH3:12][O-:13].[Na+]>CO>[CH3:12][O:13][CH2:7][C:6]1[CH:9]=[CH:10][CH:11]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1
Reactant: C[O-]
Reactant: O=[N+]([O-])c1cccc(CCl)c1
Agent: [Na+]
Solvent: CO
Product: COCc1cccc([N+](=O)[O-])c1

Procedure:
A 500-milliliter flask equipped with a reflux condenser and a magnetic stirring bar was charged with 17.1 grams (0.1 mole) of 3-nitrobenzyl chloride in 200 milliliters of methanol. To this stirred solution was added 10.8 grams (0.2 mole) of sodium methoxide. Exothermic heating was observed. The reaction mixture was heated to reflux and maintained at reflux for 22 hours. The reaction mixture was then cooled, filtered, and the filtrate was transferred to a separatory funnel wherein it was diluted with 400 milliliters of ethyl acetate and consecutively extracted with 400 milliliters of water and 400 milliliters of saturated brine respectively. The organic phase was separated, dried over magnesium sulfate, and concentrated on a rotary evaporator at 55° C., leaving a brown liquid. The brown liquid was charged to a distillation flask and distilled at a pressure of 2.3 millimeters of mercury. A main fraction (15.1 grams) was collected, said fraction having a boiling point of 118°-120° C. at 2.3 mm Hg pressure. This main fraction was identified by NMR spectroscopy as 1-(methoxymethyl)-3-nitrobenzene.
Reaction SMILES: [O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][P:24](=[O:31])([O:28]CC)[O:25]CC.Br[Si](C)(C)C.O>ClCCl.CO>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][P:24](=[O:25])([OH:31])[OH:28]
Reactant: CCOP(=O)(CCCCCCCCCCCCN1C(=O)c2ccccc2C1=O)OCC
Agent: C[Si](C)(C)Br
Solvent: O
Solvent: ClCCl
Solvent: CO
Product: O=C1c2ccccc2C(=O)N1CCCCCCCCCCCCP(=O)(O)O
Reaction time: 8 h
Yield: 97.6 %

Procedure:
Diethyl 12-(1,3-dioxoisoindolin-2-yl)dodecylphosphonate (2.00 g, 4.43 mmol) was dissolved in dry dichloromethane (25 mL). Bromotrimethylsilane (1.8 mL, 14.2 mmol) was added via syringe. The reaction was capped with a greased glass stopper and allowed to stir overnight. The volatiles were removed under reduced pressure to yield a yellow oil. This was dissolved in 10:1 methanol:water (20 mL) and allowed to stir overnight. After removing the solvents, recrystallization in acetonitrile yielded a white powdery solid (1.709 g, 98% yield). 1H NMR (400.14 MHz, DMSO) δ 7.84 (m, 4H), 3.54 (t, J=7.1 Hz, 2H), 1.58-1.53 (m, 2H), 1.50-1.31 (m, 4H), 1.30-1.20 (m, 16H). 13C {1H} NMR (100.62 MHz, DMSO) δ 167.9 (2C), 134.4 (2C), 131.6 (2C), 123.0 (2C), 37.36, 30.08 (d, J=15.8 Hz), 28.99, 28.95, 28.87 (2C), 28.70, 28.53, 27.85, 27.54 (d, J=136.5 Hz), 26.22, 22.73, (d, J=4.58 Hz). 31P {1H} NMR (161.97 MHz, DMSO): δ 27.74. MS (FAB, m/z): 396.2 (M+, 100%). Exact mass calculated (found) for [M+H]+, m/z): 396.19399 (396.19445). Analysis calculated (found) %: C 60.75 (60.64), H 7.65 (7.80).
Reaction SMILES: C(O)C.C1COCC1.[CH2:9]([CH:14]1[CH2:19][CH2:18][CH:17]([CH2:20][CH2:21][C:22]2[CH2:27][CH2:26][CH:25]([CH:28]3[CH2:33][CH2:32][C:31](=[O:34])[CH2:30][CH2:29]3)[CH2:24][CH:23]=2)[CH2:16][CH2:15]1)[CH2:10][CH2:11][CH2:12][CH3:13].[BH4-].[Na+]>O>[CH2:9]([CH:14]1[CH2:15][CH2:16][CH:17]([CH2:20][CH2:21][C:22]2[CH2:27][CH2:26][CH:25]([CH:28]3[CH2:33][CH2:32][CH:31]([OH:34])[CH2:30][CH2:29]3)[CH2:24][CH:23]=2)[CH2:18][CH2:19]1)[CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: CCCCCC1CCC(CCC2=CCC(C3CCC(=O)CC3)CC2)CC1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Solvent: C1CCOC1
Product: CCCCCC1CCC(CCC2=CCC(C3CCC(O)CC3)CC2)CC1
Temperature: 0 °C
Reaction time: 1 h
Yield: 40.7 %

Procedure:
To 1 l of mixed solvent of ethanol/THF (4/1) was dissolved 15.0 g (41.8 mmol) of the 4-(4-(2-(4-n-pentylcyclohexyl)ethyl)-3-cyclohexenyl)cyclohexanone described above, and the solution was cooled down to 0° C. To this mixture was gradually added 0.80 g (21.1 mmol) of sodium borohydride such that the liquid temperature did not exceed 15° C., and the mixture was stirred for 1 hour. Water in an amount of 350 ml was added to the reaction solution, the product thus formed was extracted with ether, the extract was washed with 1N-hydrochloric acid and water in this turn, and then the solvent was distilled off. After the residue was purified by column chromatography on silica gel (eluent: heptane/ethyl acetate=3/1), the solvent was distilled off. The residue was recrystallized from ethanol to give 6.0 g (17 mmol) of 4-(4-(2-(4-n-pentyl-cyclohexyl)ethyl)-3-cyclohexenyl)cyclohexanol. Yield of this compound based on 4-(4-(2-(4-n-pentylcyclohexyl)ethyl)-3-cyclohexenyl)cyclohexanone was 41%.
Reaction SMILES: [CH2:1]=[C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[CH:8]1[C:13]([OH:14])=[CH:12][CH:11]=[C:10]([Br:15])[CH:9]=1>>[Br:15][C:10]1[CH:11]=[CH:12][C:13]([OH:14])=[C:8]([C:2]2([CH3:1])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]2)[CH:9]=1
Reactant: Oc1ccc(Br)cc1
Reactant: C=C1CCCCC1
Product: CC1(c2cc(Br)ccc2O)CCCCC1
Temperature: 80 °C
Yield: 18.6 %

Procedure:
A mixture of methylene cyclohexane (0.96 g, 10 mmoles), p-bromophenol (1.73 g, 10 mmoles) and acid resin (Dowex 50×12--150 mg) is heated at 80° C. for 16 hours. The residue is purified by silica gel chromatography (eluant: 50/50 mixture of CH2Cl2 /hexane). On evaporation of the solvents 0.50 g (19% yield) of 4-bromo-2-(1-methylcyclohexyl) phenol in the form of a yellowish oil is obtained.
Reaction SMILES: C(OC(=O)[NH:10][C:11]1[CH:16]=[CH:15][C:14]([F:17])=[C:13]([C:18]([C:20]2[C:28]3[C:23](=[N:24][CH:25]=[C:26]([C:29]#[N:30])[CH:27]=3)[NH:22][CH:21]=2)=[O:19])[C:12]=1[F:31])C1C=CC=CC=1.C(#N)C.C[Si](I)(C)C>CO>[NH2:10][C:11]1[C:12]([F:31])=[C:13]([C:14]([F:17])=[CH:15][CH:16]=1)[C:18]([C:20]1[C:28]2[C:23](=[N:24][CH:25]=[C:26]([C:29]#[N:30])[CH:27]=2)[NH:22][CH:21]=1)=[O:19]
Reactant: N#Cc1cnc2[nH]cc(C(=O)c3c(F)ccc(NC(=O)OCc4ccccc4)c3F)c2c1
Agent: C[Si](C)(C)I
Solvent: CC#N
Solvent: CO
Product: N#Cc1cnc2[nH]cc(C(=O)c3c(F)ccc(N)c3F)c2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 60.2 %

Procedure:
To a reaction vessel, [3-(5-cyano-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-carbamic acid benzyl ester (27, 1.78 g, 4.12 mmol), 36 mL of anhydrous acetonitrile and trimethylsilyl iodide (3.29 g, 16.47 mmol) were added under nitrogen and the reaction was stirred at room temperature overnight. The reaction mixture was diluted with 20 mL of methanol and the solvents removed under vacuum. The residue was diluted with 50 mL of 2 M sodium hydroxide, and extracted with 3×50 mL of ethyl acetate. The organic layers were combined and washed with 200 mL of 10% sodium thiosulfate, then 200 mL of brine, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The crude material was slurried in methanol, the solids collected by filtration and dried to give the desired compound (28, 0.74 g, 60%).
Reaction SMILES: [F:1][CH2:2][C@@H:3]1[C@@H:7]([C:8]2[CH:13]=[CH:12][C:11]([C:14]#[C:15][Si](C)(C)C)=[CH:10][CH:9]=2)[O:6][C:5]([CH3:21])([CH3:20])[N:4]1[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].C(=O)=O.CC(C)=O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[C:14]([C:11]1[CH:10]=[CH:9][C:8]([C@H:7]2[O:6][C:5]([CH3:21])([CH3:20])[N:4]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@@H:3]2[CH2:2][F:1])=[CH:13][CH:12]=1)#[CH:15]
Reactant: CC(C)(C)OC(=O)N1[C@H](CF)[C@@H](c2ccc(C#C[Si](C)(C)C)cc2)OC1(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C=O
Agent: [F-]
Solvent: C1CCOC1
Solvent: CC(C)=O
Product: C#Cc1ccc([C@H]2OC(C)(C)N(C(=O)OC(C)(C)C)[C@@H]2CF)cc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 98.8 %

Procedure:
To a THF (20 ml) solution of (4S,5R)-tert-butyl 4-(fluoromethyl)-2,2-dimethyl-5-(4-((trimethylsilyl)ethynyl)phenyl)oxazolidine-3-carboxylate (1.65 g, 4.1 mmol) that had been cooled to −78° C. (dry ice/acetone) is added tetra-n-butyl-ammonium fluoride (5 ml of 1M solution in tetrahydrofuran, 5 mmol). The reaction is stirred at −78° C. for 1 hour. The reaction mixture is quenched (while at −78° C.) by the addition of saturated aqueous ammonium chloride solution (2 ml). The reaction mixture is warmed to room temperature and diluted with ethyl acetate (50 ml). The organic phase is washed with water (3×25 ml), dried over sodium sulfate and the volatiles removed by evaporation to give the title product (1.35 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:7]([O:8][CH3:9])=[CH:6][S:5][CH:4]=1.OS([O-])(=O)=O.[Na+].[CH:16](=O)[CH2:17][CH2:18][CH2:19][CH2:20]C>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[C:7]([O:8][CH2:9][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])=[CH:6][S:5][CH:4]=1
Reactant: COc1cscc1OC
Reactant: CCCCCC=O
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CCCCCCOc1cscc1OC

Procedure:
10 g of 3,4-dimethoxythiophene were dissolved in 10 cm3 of 1-hexanone and 30 cm3 of toluene, 0.5 g of NaHSO4 was added, and the mixture was heated to reflux. 6 cm3 of azeotrope were distilled off and the batch was then worked up as in Example 14. Fractionation gave 3.7 g of 3-methoxy-4-hexyloxythiophene, b.p. 80° to 85° C./0.1 mbar. 4 g of dihexyloxythiophene were obtained from the distillation residue by chromatography through SiO2 using CH2Cl2.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([O:19][CH2:20][O:21][CH3:22])=[C:7]([C:9]2[O:10][C:11]3[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[C:12]=3[N:13]=2)[CH:8]=1.[CH3:23][O:24]COC1C=CC(C=NC2C(C)=CC=CC=2O)=CC=1>>[CH3:23][O:24][C:4]1[C:3]([O:2][CH3:1])=[CH:8][C:7]([C:9]2[O:10][C:11]3[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[C:12]=3[N:13]=2)=[C:6]([O:19][CH2:20][O:21][CH3:22])[CH:5]=1
Reactant: COCOc1ccc(C=Nc2c(C)cccc2O)cc1
Reactant: COCOc1ccc(OC)cc1-c1nc2c(C)cccc2o1
Product: COCOc1cc(OC)c(OC)cc1-c1nc2c(C)cccc2o1

Procedure:
2-(4,5-dimethoxy-2-methoxymethoxyphenyl)-4-methylbenzoxazole (F9) was prepared in a similar manner for the preparation of 2-(5-methoxy-2-methoxymethoxyphenyl)-4-methylbenzoxazole (F8) by using 2-[(4-methoxymethoxybenzylidene)amino]-3-methylphenol (F6) (3.31 g, 10 mmol) instead of 2-[(5-methoxy-2-methoxymethoxybenzylidene)amino]-3-methylphenol (F4) in 62% (2.07 g): 1H-NMR (400 MHz, CDCl3) δ2.66 (s, 3H), 3.58 (s, 3H), 3.95 (s, 3H), 3.97 (s, 3H), 5.28 (s, 2H), 6.84 (s, 1H), 7.12 (d, 1H, J=8.0 Hz), 7.21 (t, 1H, J=8.0 Hz), 7.39 (d, 1H, J=8.0 Hz), 7.63 (s, 1H).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH:2]1[C:7]([NH2:9])=[O:8].COCCO.[CH3:15][C:16](=O)[CH3:17]>>[CH3:15][C:16]1([CH3:17])[N:1]2[CH2:6][CH2:5][NH:4][CH2:3][CH:2]2[C:7](=[O:8])[NH:9]1
Reactant: CC(C)=O
Reactant: NC(=O)C1CNCCN1
Solvent: COCCO
Product: CC1(C)NC(=O)C2CNCCN21
Yield: 64 %

Procedure:
To a stirred and warm solution of 3 parts of 2-piperazinecarboxamide in 16 parts of 2-methoxyethanol were added 51.2 parts of 2-propanone. The whole was stirred and refluxed for 20 hours. The reaction mixture was evaporated. The solid residue was crystallized from acetonitrile, yielding 2.5 parts (64%) of hexahydro-3,3-dimethylimidazo[1,5-a]pyrazin-1(5H)-one; mp. 174.2° C. (intermediate 83).
Reaction SMILES: [F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([C:9]2[CH2:13][C:12]3([C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[C:15](=[O:22])[O:14]3)[O:11][N:10]=2)[CH:6]=[CH:7][CH:8]=1.OS(O)(=O)=O>C(O)CCCC>[F:23][C:2]([F:24])([F:1])[C:3]1[CH:4]=[C:5]([C:9]2[CH:13]=[C:12]([C:21]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[C:15]([O:14][CH2:7][CH2:8][CH2:3][CH2:4][CH3:5])=[O:22])[O:11][N:10]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: O=C1OC2(CC(c3cccc(C(F)(F)F)c3)=NO2)c2ccccc21
Agent: O=S(=O)(O)O
Solvent: CCCCCO
Product: CCCCCOC(=O)c1ccccc1-c1cc(-c2cccc(C(F)(F)F)c2)no1
Temperature: 0 °C

Procedure:
A solution of 3'-(m-trifluoromethylphenyl)-spiro[isobenzofuran-1(3H),5'(4'H)-isoxazol]-3-one (10 g., 0.03 mole) and concentrated H2SO4 (1 ml.) in n-pentyl alcohol (150 ml.) was held at reflux for 14 hours, cooled and poured into 300 ml. of ice water. The mixture was extracted with 600 ml. of ether. The ethereal solution was washed two times with water, dried over CaSO4 and concentrated under vacuum to give 12.05 g. of product as a yellow oil (99%). The oil was chromatographed on silica gel using ethyl acetate as the eluant. 8.4 g. of colorless oil was collected; ir (CHCl3) 1725 cm-1 ; nD25 =1.537.
Reaction SMILES: [CH3:1][S:2]([O:5][CH:6]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7]1)(=[O:4])=[O:3].C1(CN2CCC(O)C2)C=CC=CC=1>>[CH3:1][S:2]([O:5][C@@H:6]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7]1)(=[O:3])=[O:4]
Reactant: CS(=O)(=O)OC1CCN(Cc2ccccc2)C1
Agent: OC1CCN(Cc2ccccc2)C1
Product: CS(=O)(=O)O[C@@H]1CCN(Cc2ccccc2)C1

Procedure:
(rac)-3-methanesulfonyloxy-1-(phenylmethyl)-pyrrolidine, M.S. (C.I) (M/Z): 256 [M+H]+, starting from (rac)-1-(phenylmethyl)-3-pyrrolidinol.
Reaction SMILES: [CH3:1][CH:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][C:6]([CH3:12])=[CH:7][CH:8]=2)[NH:3]1.C(=O)([O-])[O-].[K+].[K+].I[CH:20]([CH3:22])[CH3:21].ICCC>O>[CH3:1][CH:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][C:6]([CH3:12])=[CH:7][CH:8]=2)[N:3]1[CH:20]([CH3:22])[CH3:21]
Reactant: Cc1ccc2c(c1)NC(C)CC2
Reactant: CC(C)I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCCI
Solvent: O
Product: Cc1ccc2c(c1)N(C(C)C)C(C)CC2
Yield: 57.6 %

Procedure:
A mixture of 2,7-dimethyl-1,2,3,4-tetrahydroquinoline (32.2 g, 0.2 m), potassium carbonate (15.0 g, 0.11 m), and 2-iodopropane (51 g, 0.3 m) was heated at 90°-95° C. for 5.5 hr. Progress of the reaction was slow. An additional quantity (34.0 g) of iodopropane was added and the mixture refluxed for 24 hrs. longer. Starting material was still evident by thin-layer chromatography. The reaction mixture was drowned into 200 ml water and extracted with chloroform (50 ml). The organic layer was treated with 10 ml of acetic anhydride for 1 hr. at 90°-95° C. to convert the 2,7-dimethyl-1,2,3,4-tetrahydroquinoline into N-acetyl-2,7-dimethyl-1,2,3,4-tetrahydroquinoline, which enables the recovery of the pure product by distillation. The organic layer was distilled under vacuum to give 23.4 g (55% yield) of product which boiled at 85° C. at 0.21.1 mm Hg.