Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([Si:5]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[O:6][CH2:7][CH2:8][C:9]1[C:10](=[O:34])[NH:11][C:12]2[C:17]([C:18]=1[C:19]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=1[O:26][C:27](=[O:29])[CH3:28])=[CH:16][C:15]([C:30]([F:33])([F:32])[F:31])=[CH:14][CH:13]=2)([CH3:4])([CH3:3])[CH3:2].CI.[C:49]([O-])([O-])=O.[K+].[K+]>CC(C)=O.C(OCC)(=O)C>[C:1]([Si:5]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)([C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)[O:6][CH2:7][CH2:8][C:9]1[C:10](=[O:34])[N:11]([CH3:49])[C:12]2[C:17]([C:18]=1[C:19]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=1[O:26][C:27](=[O:29])[CH3:28])=[CH:16][C:15]([C:30]([F:31])([F:33])[F:32])=[CH:14][CH:13]=2)([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(=O)Oc1ccc(Cl)cc1-c1c(CCO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c(=O)[nH]c2ccc(C(F)(F)F)cc12
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: CC(=O)Oc1ccc(Cl)cc1-c1c(CCO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c(=O)n(C)c2ccc(C(F)(F)F)cc12
Reaction time: 18 h

Procedure:
A suspension of the product from step A (6.82 g, 10.3 mmol), methyl iodide (4.37 g, 30.8 mmol) and K2CO3 (3.05 g, 30.8 mmol) in acetone (200 mL) at ambient temperature was stirred for 18 hours. At the end diluted with ethyl acetate (200 mL), washed with water (100 mL), brine (100 mL) and dried. Chromatography with gradient elution (SiO2) using hexanes, ethyl acetate (90:10 to 70:30) afforded the compound of Step B as the major product (5.52 g, 8.1 mmol, 79%, Rt=2.3 minutes C18 LC) as white solid. MS [M+H]=678. 1H NMR (CD3OD) δ 7.82 (d, J=8.1 Hz, 1H), 7.73 (d, J=8.9 Hz, 1H), 7.52 (d, J=9.2 Hz, 1H), 7.48 (m, 4H), 7.34 (m, 3H), 7.21 (m, 6H), 3.91 (m, 1H), 3.76 (m, 4H), 2.88 (m, 1H), 2.70 (m, 1H), 1.71 (s, 3H), 0.94 (s, 9H). A minor product characterized as the O-methyl derivative had the following characteristics. MS [M+H]=678. 1H NMR (CD3OD) δ 7.82 (d, J=8.1 Hz, 1H), 7.95 (d, J=5.1 Hz, 1H), 7.52 (d, J=9.2 Hz, 1H), 7.48 (m, 4H), 7.34 (m, 3H), 7.21 (m, 6H), 3.91 (m, 1H), 3.76 (m, 4H), 2.88 (m, 1H), 2.70 (m, 1H), 1.71 (s, 3H), 0.94 (s, 9H). The ratio of the N-methyl derivative to the O-methyl derivative was approximately 9:1.
Reaction SMILES: [C:1]([O:4][C:5]1[C:6](=[O:13])[CH:7]([CH3:12])[O:8][C:9]=1[CH2:10]C)(=[O:3])[CH3:2].[C:14](Cl)(=O)C>>[C:1]([O:4][C:5]1[C:6](=[O:13])[CH:7]([CH2:12][CH3:14])[O:8][C:9]=1[CH3:10])(=[O:3])[CH3:2]
Reactant: CCC1=C(OC(C)=O)C(=O)C(C)O1
Reactant: CC(=O)Cl
Product: CCC1OC(C)=C(OC(C)=O)C1=O

Procedure:
A mixture (1.08 g) of 4-acetoxy-2-ethyl-5-methyl-3(2H)-furanone (major) and 4-acetoxy-5-ethyl-2-methyl-3(2H)-furanone (minor) was obtained by the same method as in Preparation Example 2 except that 0.54 ml of acetyl chloride was used rather than 0.95 ml of pivaloyl chloride.
Reaction SMILES: [N:1]([CH2:4][CH:5]([C:7]1[CH:12]=[CH:11][C:10]([S:13][CH3:14])=[CH:9][CH:8]=1)[OH:6])=[N+]=[N-].C([O-])=O.[NH4+]>[Pd].CO>[NH2:1][CH2:4][CH:5]([C:7]1[CH:12]=[CH:11][C:10]([S:13][CH3:14])=[CH:9][CH:8]=1)[OH:6]
Reactant: CSc1ccc(C(O)CN=[N+]=[N-])cc1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CO
Product: CSc1ccc(C(O)CN)cc1
Temperature: 64 °C
Yield: 72 %

Procedure:
To a stirred rt suspension consisting of 2-azido-1-(4-methylsulfanyl-phenyl)-ethanol (104.6 mg, 0.50 mmol), 10% Pd/C (100 mg, 0.10 mmol) and MeOH (25 mL) was added ammonium formate (316 mg, 5.0 mmol) under a N2 atmosphere. The resulting mixture was heated at 64° C. for 2 h. After cooling to rt, the catalyst was removed by filtration through a pad of celite and the celite pad washed with MeOH. The filtrate was concentrated and purified (FCC) to yield the title compound (66 mg, 72%).
Reaction SMILES: C(O)=O.C(N(CC)CC)C.ClCCl.[CH3:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH2:17][CH2:18][C:19]2=[O:24]>O>[CH3:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH2:17][CH2:18][C@@H:19]2[OH:24]
Reactant: Cc1cccc2c1CCC2=O
Solvent: ClCCl
Solvent: O=CO
Solvent: O
Product: Cc1cccc2c1CC[C@@H]2O
Temperature: 25 °C
Reaction time: 2 h
Yield: 92.7 %

Procedure:
To a mixture of formic acid (0.91 mL, 23.9 mmol) and triethylamine (0.29 mL, 21.0 mmol), a dichloromethane (6.0 mL) solution of 4-methylindan-1-one (1.00 g, 6.84 mmol) was added, and chloro[(1S,2S)—N-(p-toluenesulfonyl)-1,2-diphenyl ethanediamine](mesitylene)ruthenium(II) (128 mg, 0.210 mmol) was added thereto at room temperature, and then, the resulting mixture was stirred under a nitrogen atmosphere at room temperature for 2 hours. Water was added to the reaction solution, and the organic matter was extracted with ethyl acetate. The organic layer was washed with a saturated sodium bicarbonate solution and a saturated sodium chloride solution, then dried over anhydrous sodium sulfate and filtered. Then, the solvent was distilled off under reduced pressure, whereby a crude product was obtained. This crude product was purified by silica gel column chromatography (hexane:ethyl acetate=100:0 to 75:25 (v/v)), whereby the objective title compound was obtained as a white solid (0.94 g, yield: 93%).
Reaction SMILES: [BH4-].[Na+].[B-](F)(F)(F)[O+](C)C.[C:10]([CH2:13][S:14][CH2:15][C@@H:16]1[CH2:20][C@@H:19]([OH:21])[CH2:18][N:17]1[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=1)=[O:23])(=O)[NH2:11].Cl.CO.[O-:38][C:39]#[N:40].[K+]>O1CCCC1.CO.O>[NH:11]([CH2:10][CH2:13][S:14][CH2:15][C@@H:16]1[CH2:20][C@@H:19]([OH:21])[CH2:18][N:17]1[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=1)=[O:23])[C:39]([NH2:40])=[O:38]
Reactant: N#C[O-]
Reactant: NC(=O)CSC[C@@H]1C[C@@H](O)CN1C(=O)OCc1ccc([N+](=O)[O-])cc1
Agent: C[O+](C)[B-](F)(F)F
Agent: Cl
Agent: [BH4-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: NC(=O)NCCSC[C@@H]1C[C@@H](O)CN1C(=O)OCc1ccc([N+](=O)[O-])cc1
Reaction time: 8 h
Yield: 63.4 %

Procedure:
To a solution of sodium borohydride (0.78 g) in tetrahydrofuran (25 ml) was added dropwise boron trifluoride dimethyl etherate (8.78 ml) with stirring under ice-cooling and the solution was stirred at the same temperature for 10 minutes. To this solution was added (2S,4R)-2-(carbamoylmethyl)thiomethyl-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (2.53 g) and the mixture was stirred at ambient temperature for 4 hours. To the reaction mixture was added methanol (5 ml) and the mixture was filtered. The filtrate was evaporated in vacuo to give a residue. The residue was dissolved in methanol (30 ml). To the solution was added 10% hydrogen chloride-methanol solution (10 ml) and the mixture was allowed to stand overnight at ambient temperature. The reaction mixture was evaporated in vacuo to give a residue. The residue was dissolved in a mixture of tetrahydrofuran (30 ml) and water (15 ml). To the solution was added a solution of potassium cyanate (3.83 g) in water (10 ml) and the mixture was stirred at 50°-60° C. for 30 minutes. The reaction mixture was evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of chloroform and methanol (9:1, v/v). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4R)-2-(2-ureidoethyl)thiomethyl-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.73 g).
Reaction SMILES: [CH3:1][Mg]Br.[Cl:4][C:5]1[CH:12]=[C:11]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][C:18]=2[CH:19]=[O:20])[CH:10]=[CH:9][C:6]=1[C:7]#[N:8]>C1COCC1>[Cl:4][C:5]1[CH:12]=[C:11]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][C:18]=2[CH:19]([OH:20])[CH3:1])[CH:10]=[CH:9][C:6]=1[C:7]#[N:8]
Reactant: N#Cc1ccc(-c2cnccc2C=O)cc1Cl
Reactant: C[Mg]Br
Solvent: C1CCOC1
Product: CC(O)c1ccncc1-c1ccc(C#N)c(Cl)c1
Temperature: 0 °C
Yield: 89.4 %

Procedure:
A solution of methylmagnesium bromide (519 μl, 1.558 mmol) was added dropwise to a solution of 2-chloro-4-(4-formylpyridin-3-yl)benzonitrile (126 mg, 0.519 mmol) in dry THF (15 mL) at −50° C. The resulting mixture was slowly warmed up to 0° C. during 2 hr. The reaction was quenched by NH4Cl (solution). After extraction with CH2Cl2, dry over Na2SO4, filtration, concentration again, the residue was purified by column (CH2Cl2-MeOH, v/v, 1-3.5%) and yielded 120 mg of 2-chloro-4-(4-(1-hydroxyethyl)pyridin-3-yl)benzonitrile. ESI-MS m/z: 259 [M+1]+, Retention time 1.11 min; 1H-NMR (MeOD, 400 MHz) δ 1.29 (d, J=6.4 Hz, 3H), 4.83 (q, J=6.4 Hz, 1H), 7.50 (dd, J=8.0, 1.6 Hz, 1H), 7.71 (d, J=1.6 Hz, 1H), 7.73 (d, J=5.6 Hz, 1H), 7.92 (d, J=8.0 Hz, 1H), 8.35 (s, 1H), 8.61 (d, J=5.6 Hz, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:14]=1[S:13][CH2:12][CH2:11][C:10]2=[O:15])=[O:4].[BH4-].[Na+]>C(O)C>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:14]=1[S:13][CH2:12][CH2:11][CH:10]2[OH:15])=[O:4]
Reactant: COC(=O)c1cccc2c1SCCC2=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: COC(=O)c1cccc2c1SCCC2O
Reaction time: 1 h
Yield: 98.9 %

Procedure:
Methylthiochroman-4-one-8-carboxylate (0.500 g, 2.25mmol) was dissolved with stirring in ethanol (20 ml) and treated with sodium borohydride (0.085 g, 2.25 mmol). After 1 h, the reaction mixture was evaporated under reduced pressure and the residue partitioned between ethyl acetate and water. The aqueous layer was then extracted with ethyl acetate (1 x) and the combined organic layers were dried (Na2SO4) and evaporated under reduced pressure to give a yellow oil, which was purified by silica-gel chromatography (1:1 Pentane:EtOAc as eluant) to give the title compound as a colourless oil (0.499 g, 99%)
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([CH:5]=[CH:6]1)[CH2:3][CH:2]2[S:8]([NH2:11])(=[O:10])=[O:9].C(=O)(O)[O-:13].[Na+].ClCCl.ClC1C=CC=C(C(OO)=O)C=1>O>[O:13]1[CH:6]2[CH:5]1[CH:4]1[CH2:7][CH:1]2[CH:2]([S:8]([NH2:11])(=[O:9])=[O:10])[CH2:3]1
Reactant: NS(=O)(=O)C1CC2C=CC1C2
Reactant: O=C([O-])O
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: NS(=O)(=O)C1CC2CC1C1OC21
Temperature: 5 °C
Reaction time: 0.33 h
Yield: 63.1 %

Procedure:
To a four-necked flask having an inner volume of 500 ml and equipped with an electromagnetic stirring device, a nitrogen inlet tube, and a thermometer, there were charged 10.0 g (57.7 mmol) of 5-norbornene-2-sulfonamide, 15.1 g (180.0 mmol) of sodium bicarbonate, and 200 g of dichloromethane. After cooling the mixture to 5° C., 14.8 g (60.0 mmol) of 70% m-chloroperbenzoic acid was added thereto over a 20 minute period, and the mixture was stirred at 5° C. for 2 hours. To the reaction mixture was added 100 g of distilled water, and the mixture was separated into an organic layer and an aqueous layer. The organic layer was washed with 40 g of distilled water and concentrated under reduced pressure. By recrystallizing the residue obtained from ethyl acetate, there was obtained 6.89 g (36.4 mmol) of 5,6-epoxy-2-norbornanesulfonamide represented by the following formula (yield 63%):
Reaction SMILES: NC1C=C([F:11])C=CC=1C([O-])=O.[C:12]([N:15]([CH2:34][C:35]1[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[C:37]([C:45]([F:48])([F:47])[F:46])[CH:36]=1)[CH:16]1[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[C:18]2[CH:29]=[C:30](Br)[CH:31]=[CH:32][C:17]1=2)(=[O:14])[CH3:13]>>[C:12]([N:15]([CH2:34][C:35]1[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[C:37]([C:45]([F:48])([F:47])[F:46])[CH:36]=1)[CH:16]1[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[C:18]2[CH:29]=[C:30]([F:11])[CH:31]=[CH:32][C:17]1=2)(=[O:14])[CH3:13]
Reactant: CC(=O)N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)C1CCCN(C(=O)OC(C)C)c2cc(Br)ccc21
Reactant: Nc1cc(F)ccc1C(=O)[O-]
Product: CC(=O)N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)C1CCCN(C(=O)OC(C)C)c2cc(F)ccc21

Procedure:
This compound was prepared utilizing the same methodology described in Example 22 by replacement of methyl 2-amino-4-bromobenzoate with 2-amino-4-fluorobenzoate following the procedure of Example 22, Steps 1-6 for the synthesis of isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate. EI MS 535 (M+H).
Reaction SMILES: [N:1]([C:4]([CH3:54])([CH3:53])[CH2:5][C@@H:6]1[NH:11][CH2:10][C@H:9]([O:12][CH:13]([C:24]2[CH:25]=[CH:26][C:27]3[O:32][CH2:31][CH2:30][N:29]([CH2:33][CH2:34][CH2:35][O:36][CH3:37])[C:28]=3[CH:38]=2)S(C2C=CC(C)=CC=2)(=O)=O)[C@@H:8]([C:39]2[CH:44]=[CH:43][C:42]([CH2:45][O:46][CH2:47][C@H:48]([O:50][CH2:51][CH3:52])[CH3:49])=[CH:41][CH:40]=2)[CH2:7]1)=[C:2]=[O:3].[CH2:55](O)C1C=CC=CC=1>>[CH2:51]([O:50][C@H:48]([CH3:49])[CH2:47][O:46][CH2:45][C:42]1[CH:41]=[CH:40][C:39]([C@@H:8]2[C@@H:9]([O:12][CH2:13][C:24]3[CH:25]=[CH:26][C:27]4[O:32][CH2:31][CH2:30][N:29]([CH2:33][CH2:34][CH2:35][O:36][CH3:37])[C:28]=4[CH:38]=3)[CH2:10][NH:11][C@@H:6]([CH2:5][C:4]([NH:1][C:2](=[O:3])[CH3:55])([CH3:53])[CH3:54])[CH2:7]2)=[CH:44][CH:43]=1)[CH3:52]
Reactant: OCc1ccccc1
Reactant: CCO[C@H](C)COCc1ccc([C@H]2C[C@H](CC(C)(C)N=C=O)NC[C@@H]2OC(c2ccc3c(c2)N(CCCOC)CCO3)S(=O)(=O)c2ccc(C)cc2)cc1
Product: CCO[C@H](C)COCc1ccc([C@H]2C[C@H](CC(C)(C)NC(C)=O)NC[C@@H]2OCc2ccc3c(c2)N(CCCOC)CCO3)cc1
Temperature: 115 °C

Procedure:
A mixture of 1.0 mmol of 6-[(3R,4R,6R)-6-(2-isocyanato-2-methyl-propyl)-4-[4-((R)-2-ethoxy-propoxymethyl)-phenyl]-1-(toluene-4-sulfonyl)-piperidin-3-yloxymethyl]-4-(3-methoxy-propyl) -3,4-dihydro-2H-benzo[1,4]oxazine and 20.0 mmol of benzyl alcohol is heated at 115° C. for 14 h. The reaction mixture is directly purified by flash chromatography (SiO2 60 F) to afford the title compound which is identified based on its Rf value.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][OH:10].[O:11]1[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12]1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][O:10][CH:12]1[CH2:13][CH2:14][CH2:15][CH2:16][O:11]1
Reactant: C1=COCCC1
Reactant: OCCc1ccccc1Br
Agent: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: Brc1ccccc1CCOC1CCCCO1
Temperature: 25 °C
Reaction time: 2 h
Yield: 97.1 %

Procedure:
To a solution of 2-(2-bromo-phenyl)-ethanol (5.0 g, 24.9 mmol, 1.0 eq) in DCM (100 mL) was added 3,4-dihydro-2H-pyran (3.4 mL, 37.3 mmol, 1.5 eq.), followed by camphorsulfonic acid (2100 mg). The mixture was stirred at room temperature for 2 h. After adding K2CO3 (300 mg), the mixture was filtered to remove the precipitate, the filtrate was washed with H2O (100 mL), brine (100 mL). The organic phase was dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The oily residue was applied to silica chromatography eluting with EtOAc/Heptanes (0:100 to 50:50) to give 2-[2-(2-bromo-phenyl)-ethoxy]-tetrahydro-pyran as a colorless oil. 1H NMR (chloroform-d) δ: 7.48-7.54 (m, 1H), 7.25-7.30 (m, 1H), 7.17-7.23 (m, 1H), 7.01-7.09 (m, 1H), 4.56-4.61 (m, 1H), 3.88-3.97 (m, 1H), 3.58-3.67 (m, 1H), 3.04 (t, J=7.2 Hz, 2H), 1.62-1.67 (m, 1H), 1.41-1.60 (m, 5H), 0.85-0.90 (m, 1H). Amount obtained: 6.9 g, 97.1% yield.
Reaction SMILES: [H-].[Na+].[C:3]([NH:5][C:6](=[N:8][CH3:9])[CH3:7])#[N:4].[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17]Cl)=[CH:13][N:12]=1>CN(C)C=O>[C:3]([N:5]([CH2:17][C:14]1[CH:15]=[CH:16][C:11]([Cl:10])=[N:12][CH:13]=1)[C:6](=[N:8][CH3:9])[CH3:7])#[N:4]
Reactant: CN=C(C)NC#N
Reactant: ClCc1ccc(Cl)nc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN=C(C)N(C#N)Cc1ccc(Cl)nc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 50.3 %

Procedure:
0.6 g of sodium hydride (purity 60%) was added to the solution of 1.3 g of N-cyano-N'-methylacetamidine in 20 ml of N,N-dimethylformamide at ice bath temperature. After stirring it at the same temperature for 1 hour, 2.2 g of 2-chloro-5-pyridylmethylchloride was added to the mixture, followed by stirring for 5 hours at room temperature. The reaction mixture was then poured into ice-water, extracted with ethyl acetate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue obtained was purified by column chromatography on silica gel to afford 1.5 g of compound No. 22 m.p. 101°-103° C.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[C:9]([CH3:11])[C:8]([CH2:12][C:13](O)=[O:14])=[C:7]([CH3:16])[C:6]=1[OH:17])([CH3:4])([CH3:3])[CH3:2].CN(C)C=O.S(Cl)([Cl:25])=O>C1C=CC=CC=1>[C:1]([C:5]1[CH:10]=[C:9]([CH3:11])[C:8]([CH2:12][C:13]([Cl:25])=[O:14])=[C:7]([CH3:16])[C:6]=1[OH:17])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1cc(C(C)(C)C)c(O)c(C)c1CC(=O)O
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Solvent: c1ccccc1
Product: Cc1cc(C(C)(C)C)c(O)c(C)c1CC(=O)Cl
Reaction time: 16 h

Procedure:
47.2 g (0.20 moles) of 4-t-butyl-2,6-dimethyl-3-hydroxyphenyl acetic acid, and 0.4 ml of dry N,N-dimethylformamide are dispersed in 325 ml of dry benzene. To this slurry was added dropwise with stirring under a nitrogen atmosphere 28.5 g (17.5 ml, 0.24 moles) of thionyl chloride at ambient temperature. The reaction mixture was allowed to stir for 16 hours, then evaporated under reduced pressure, yielding an orange-colored solid, which proved by analysis to be the desired acid chloride. The residue was dissolved in 500 ml of benzene, analyzed for chloride ion and used for subsequent reactions in solution.
Reaction SMILES: N#N.[NH2:3][CH2:4][CH2:5][O:6][CH2:7][CH2:8]O.[OH-].[Na+].C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CN=C1.II.[NH:53]1[CH2:57][CH2:56][CH2:55][CH2:54]1.C([O-])([O-])=O.[K+].[K+].[ClH:64]>C1COCC1.C(Cl)Cl.CC(=O)OCC.CC(C)=O.CO>[ClH:64].[N:53]1([CH2:8][CH2:7][O:6][CH2:5][CH2:4][NH2:3])[CH2:57][CH2:56][CH2:55][CH2:54]1
Reactant: NCCOCCO
Reactant: C1CCNC1
Agent: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Agent: Cl
Agent: II
Solvent: ClCCl
Solvent: CO
Solvent: C1CCOC1
Product: NCCOCCN1CCCC1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of 2-(2-aminoethoxy)ethanol (536 mg, 5.00 mmol) in THF (3 mL) was added aq. 2M NaOH (2.6 mL, 5.20 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 10 min and a solution of di-tert-butyl dicarbonate (1.16 g, 5.20 mmol) in THF (3 mL) was then added dropwise. The reaction mixture was warmed to rt and stirred at this temperature until completion of the reaction. The mixture was diluted with CH2Cl2, filtered and the layers separated. The organic layer was dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. The crude alcohol was redissolved in dry CH2Cl2 (20 mL) and treated with triphenylphoshine on polystyrene (5.63 mmol) and imidazole (190 mg, 2.76 mmol). To this mixture cooled to 0° C. was added iodine (808 mg, 3.15 mmol). The reaction mixture was warmed to rt and stirred at this temperature until completion of the reaction. The mixture was then filtered, CH2Cl2 removed under reduced pressure. The residue was redissolved in EA, successively washed with 10% aq. Na2SO3 and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude iodide was redissolved in CH3CN (15 mL) and treated with pyrrolidine (0.17 mL, 1.99 mmol) and K2CO3 (465 mg, 3.36 mmol). The reaction mixture was stirred at rt until completion of the reaction, filtered and concentrated under reduced pressure. The amine was purified by FC (hept-EA-acetone, 1:0:0->0:0:1) and then the Boc group was removed by treatment with HCl (4.0 M in dioxane, 10 eq.) in dry CH2Cl2 (3 mL). The title compound was obtained after trituration in hot EA/acetone/MeOH as a beige solid. LC-MS-conditions 01: tR=0.13 min; [M+H]+=159.11.
Reaction SMILES: [CH2:1]([OH:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].C=CCCCCCC.CCCCCCC=CCCCCCC.[C:40](OCCCCCCCCC=C)(=[O:42])[CH3:41]>>[C:40]([O:17][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])(=[O:42])[CH3:41]
Reactant: CCCCCCC=CCCCCCCCCO
Reactant: C=CCCCCCCCCOC(C)=O
Agent: CCCCCCC=CCCCCCC
Solvent: C=CCCCCCC
Product: CCCCCCC=CCCCCCCCCOC(C)=O

Procedure:
A process for preparing 9-hexadecenyl alcohol by reacting 1-octene or 7-tetradecene with 9-decenyl acetate in accordance with the method of claim 7 to obtain 9-hexadecenyl acetate and then reacting the acetate with water to obtain the corresponding alcohol.
Reaction SMILES: [NH2:1][C:2]1[CH:12]=[CH:11][C:10]([CH:13]2[CH2:18][CH2:17][CH:16]([O:19][Si](C(C)(C)C)(C)C)[CH2:15][CH2:14]2)=[CH:9][C:3]=1[C:4]([N:6]([CH3:8])[CH3:7])=[O:5].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[NH2:1][C:2]1[CH:12]=[CH:11][C:10]([CH:13]2[CH2:18][CH2:17][CH:16]([OH:19])[CH2:15][CH2:14]2)=[CH:9][C:3]=1[C:4]([N:6]([CH3:8])[CH3:7])=[O:5]
Reactant: CN(C)C(=O)c1cc(C2CCC(O[Si](C)(C)C(C)(C)C)CC2)ccc1N
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CN(C)C(=O)c1cc(C2CCC(O)CC2)ccc1N
Temperature: 25 °C

Procedure:
A solution of 2-amino-5-(4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-N,N-dimethylbenzamide (Compound 173B, 0.320 g, 0.850 mmol) in THF (2 mL) was charged with 1.0 M of tetra-n-butylammonium fluoride in THF (8.50 mL) and stirred at rt over night. The reaction mixture was partitioned between EtOAc and water and separated. The aqueous was extracted with EtOAc (3×) and the combined organic fractions were washed with brine, dried over sodium sulfate, filtered, and concentrated. The compound was purified on an Isco Combiflash unit eluting with 75 to 100% EtOAc in heptane to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ 6.91-6.97 (m, 1H), 6.80-6.85 (m, 1H), 6.59-6.64 (m, 1H), 4.94 (s, 2H), 4.30 (d, J=3.79 Hz, 1H), 2.91 (s, 6H), 2.24-2.39 (m, 1H), 1.62-1.80 (m, 4H), 1.34-1.54 (m, 4H), 1.20-1.32 (m, 1H); MS (ES+): m/z: 263.15 [MH+]. HPLC: tR=2.84 min (Micromass ZQ3: polar—3 min).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([S:8][CH3:9])=[CH:4][CH:3]=1.[Li]C(C)(C)C.CCCCC.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[C:28](=[O:32])[CH2:29][CH2:30][CH:31]=2)=[CH:23][CH:22]=1>CCOCC>[CH3:9][S:8][C:5]1[CH:6]=[CH:7][C:2]([C:28]2([OH:32])[CH2:29][CH2:30][CH:31]=[C:27]2[C:24]2[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=2)=[CH:3][CH:4]=1
Reactant: O=C1CCC=C1c1ccc(F)cc1
Reactant: CSc1ccc(Br)cc1
Agent: [Li]C(C)(C)C
Solvent: CCCCC
Solvent: CCOCC
Product: CSc1ccc(C2(O)CCC=C2c2ccc(F)cc2)cc1
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 89.4 %

Procedure:
To a solution of 3.86 g (19 mmol) of 4-bromothioanisole in 90 mL of Et2O cooled at -78° C., was added 22 mL of 1.7M solution of t-BuLi in pentane (38 mmol) dropwise. The reaction mixture was stirred for 15 min at -78° C. and a solution of 2.23 g of 2-(4-Fluorophenyl)-2-cyclopenten-1-one in 10 mL of Et2O was added. After stirring for 15 min at -78° C., the reaction mixture was warmed to 0° C., and quenched with 50 mL of sat. NH4Cl. The product was extracted with 100 mL EtOAc, dried over Na2SO4, and purified by flash chromatography, eluted with 4:1 hexane/EtOAc to give 3.4 g of the desired product. 1H NMR (CDCl3) δ2.12 (1H, s), 2.34 (2H, m), 2.44 (3H, s), 2.45-2.52 (1H, m), 2.56-2.65 (1H, m), 6.37 (1H, m), 6.84 (2H, J=8.7 Hz, t), 7.17 (2H, J=8.3 Hz, d), 7.24-7.33 (4H, m).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]#[N:11])=[CH:4][CH:3]=1.[CH3:12][N:13]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:14](Cl)=[O:15]>>[C:10]([CH2:9][CH2:8][C:5]1[CH:4]=[CH:3][C:2]([O:1][C:14](=[O:15])[N:13]([CH3:12])[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:7][CH:6]=1)#[N:11]
Reactant: CN(C(=O)Cl)c1ccccc1
Reactant: N#CCCc1ccc(O)cc1
Product: CN(C(=O)Oc1ccc(CCC#N)cc1)c1ccccc1

Procedure:
The title product was prepared from 3-(4-hydroxyphenyl)proprionitrile and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (11%, colourless oil). HPLC-MS: m/z=281.2 (M+1); Rt: 3.75 min, purity 80%.