Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[Na+:2].[C:3]([OH:10])(=[O:9])/[CH:4]=[CH:5]/[CH:6]=[CH:7]/[CH3:8]>>[C:3]([O-:10])(=[O:9])/[CH:4]=[CH:5]/[CH:6]=[CH:7]/[CH3:8].[Na+:2]
Reactant: C/C=C/C=C/C(=O)O
Agent: [Na+]
Agent: [OH-]
Product: C/C=C/C=C/C(=O)[O-]

Procedure:
For example, Japanese Unexamined Patent Application Publication No. 54-163516 discloses a process for preparing a crystalline sorbic acid. This process includes the steps of preparing a polyester from ketene and crotonaldehyde, decomposing the polyester with hydrochloric acid in the presence of, for example, a urea compound to yield a decomposition reaction mixture, separating the decomposition reaction mixture by filtration, and washing the residue to yield a crude sorbic acid, adding a sodium hydroxide aqueous solution to the crude sorbic acid to yield a sodium sorbate aqueous solution, treating the aqueous solution with activated carbon, neutralizing and cooling the treated solution to crystallize sorbic acid. Japanese Examined Patent Application Publication No. 44-26646 discloses a process for producing a crystalline sorbic acid. The process includes the steps of preparing a polyester from ketene and crotonaldehyde, decomposing the polyester with hydrochloric acid having a concentration of 35% by weight or more at temperatures ranging from room temperature to around the boiling point of the hydrochloric acid used, cooling the reaction mixture, separating a crude sorbic acid by filtration, washing the crude sorbic acid with water, putting the washed crude sorbic acid into water, heating and dissolving the sorbic acid to yield a solution, adding activated carbon to the solution, boiling the mixture, and filtering the mixture while heating, and gradually cooling the resulting filtrate to yield a crystalline sorbic acid.
Reaction SMILES: [Br:1][C:2]1[C:3](Cl)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-].[NH4+:11].C1COCC1>O>[Br:1][C:2]1[C:3]([NH2:11])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1
Reactant: [NH4+]
Reactant: Clc1ncc(Br)c(Cl)n1
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Nc1nc(Cl)ncc1Br
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A 100 mL round bottom flask was charged with 5-bromo-2,4-dichloropyrimidine (10.0 g, 44 mmol), concentrated ammonium hydroxide (100 mL) and THF (150 mL). The resulting mixture was magnetically stirred at room temperature for 12 h. Work-up: the reaction mixture was diluted with water (100 mL) and then extracted with EtOAc (50 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel to afford 11 g (quantitative) of the product as a white solid. MS m/z: 208 (M+H+).
Reaction SMILES: [C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].Br[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][Cl:16].C(=O)([O-])[O-].[K+].[K+]>CCCCCCC>[Cl:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH:2]([C:3](=[O:4])[CH3:5])[C:1]([O:7][CH2:8][CH3:9])=[O:6]
Reactant: ClCCCCCBr
Reactant: CCOC(=O)CC(C)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCCCCCC
Product: CCOC(=O)C(CCCCCCl)C(C)=O
Temperature: 90 °C
Yield: 176 %

Procedure:
A mixture of ethyl acetoacetate [VI-1] (109.3 g), n-heptane (100 g) and 1-bromo-5-chloropentane [V-1] (185.5 g) is heated to 90° C. Thereto is added anhydrous potassium carbonate (193.5 g) in portions, and the mixture is stirred with heating at 100° C. for 14 hours. The mixture is filtered with suction, and the residue is washed with n heptane. The n-heptane layers (i.e. the above filtrate and washing liquid) are combined to give a solution (347 g) of crude ethyl 7-chloro-2-(1-oxoethyl)heptanoate [II-1] in n-heptane (content of the heptanoate; 44.3%).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:22])[CH2:5][CH2:6][N:7]([C:14](=[O:21])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][NH2:20])[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH3:2].C(N(C(C)C)CC)(C)C.[CH3:32][C@@H:33]([C@@H:40]1[C@@:44]2([CH3:62])[CH2:45][CH2:46][CH:47]3[C@@:52]4([CH3:61])[CH2:53][CH2:54][CH:55]([O:57][C:58](Cl)=[O:59])[CH2:56][C:51]4=[CH:50][CH2:49][CH:48]3[CH:43]2[CH2:42][CH2:41]1)[CH2:34][CH2:35][CH2:36][CH:37]([CH3:39])[CH3:38].Cl>ClCCl>[CH2:1]([O:3][C:4](=[O:22])[CH2:5][CH2:6][N:7]([C:14](=[O:21])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:58]([O:57][CH:55]1[CH2:56][C:51]2[C:52]([CH3:61])([CH:47]3[CH:48]([CH2:49][CH:50]=2)[CH:43]2[C:44]([CH3:62])([CH:40]([CH:33]([CH3:32])[CH2:34][CH2:35][CH2:36][CH:37]([CH3:38])[CH3:39])[CH2:41][CH2:42]2)[CH2:45][CH2:46]3)[CH2:53][CH2:54]1)=[O:59])[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH3:2]
Reactant: CCOC(=O)CCN(CC(=O)OCC)C(=O)CCCCCN
Reactant: CC(C)CCC[C@@H](C)[C@H]1CCC2C3CC=C4CC(OC(=O)Cl)CC[C@]4(C)C3CC[C@@]21C
Agent: Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)CCN(CC(=O)OCC)C(=O)CCCCCNC(=O)OC1CCC2(C)C(=CCC3C2CCC2(C)C(C(C)CCCC(C)C)CCC32)C1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
The hydrochloride salt of 3-[(6-Amino-hexanoyl)-ethoxycarbonylmethyl-amino]-propionic acid ethyl ester AC (4.7 g, 14.8 mmol) is taken up in dichloromethane. The suspension is cooled to 0° C. on ice. To the suspension diisopropylethylamine (3.87 g, 5.2 mL, 30 mmol) is added. To the resulting solution cholesteryl chloroformate (6.675 g, 14.8 mmol) is added. The reaction mixture is stirred overnight. The reaction mixture is diluted with dichloromethane and ished with 10% hydrochloric acid. The product is purified by flash chromatography (10.3 g, 92%).
Reaction SMILES: C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O.[C:12]([O:16][C:17]([N:19]1[CH2:22][CH:21]([OH:23])[CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13]>C(Cl)Cl>[O:23]=[C:21]1[CH2:22][N:19]([C:17]([O:16][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:18])[CH2:20]1
Reactant: CC(C)(C)OC(=O)N1CC(O)C1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CC(=O)C1
Reaction time: 14 h
Yield: 20 %

Procedure:
PCC (4.94 g, 22.8 mmol) was added portion wise to a stirred solution of tert-butyl-3-hydroxyazetidine-1-carboxylate (3.3 g, 19 mmol) in DCM (50 mL) at 20-35° C. and the reaction mixture was stirred continuously at the same temperature for 12-16 h. The reaction mixture was filtered and the filtrate was washed with water, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (using 60-120 silica gel and 10% EtOAc in Hexane as eluent) to afford 650 mg of the title compound.
Reaction SMILES: [CH3:1][N:2]([CH3:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7](O)=[O:8])=[CH:5][CH:4]=1.S(Cl)([Cl:15])=O>O1CCCC1>[CH3:1][N:2]([CH3:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([Cl:15])=[O:8])=[CH:5][CH:4]=1
Reactant: CN(C)c1ccc(C(=O)O)cc1
Reactant: O=S(Cl)Cl
Solvent: C1CCOC1
Product: CN(C)c1ccc(C(=O)Cl)cc1

Procedure:
To a 1000 mL round bottomed flask was added 4-dimethylamino-benzoic acid (50.0 g, 1.0 eq) and THF (600 mL). A solution of thionyl chloride (44.16 mL, 2.0 eq) in tetrahydrofuran was added and the resulting mixture heated to reflux for 4 hours. The excess thionyl chloride and solvent were removed under reduced pressure to yield 4-dimethylamino-benzoyl chloride as a solid, which was used without further purification in the preparation of compound 560.
Reaction SMILES: [S:1]1[C:5]([CH:6]=[O:7])=[CH:4][N:3]=[CH:2]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[F:26][C:27]([Si](C)(C)C)([F:29])[F:28]>C1COCC1>[F:26][C:27]([F:29])([F:28])[CH:6]([C:5]1[S:1][CH:2]=[N:3][CH:4]=1)[OH:7]
Reactant: C[Si](C)(C)C(F)(F)F
Reactant: O=Cc1cncs1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: OC(c1cncs1)C(F)(F)F
Yield: 68.9 %

Procedure:
The method described in Example 4 (step 4.5.) is followed. Starting from 2 g (17.68 mmol) of thiazole-5-carboxaldehyde, 0.88 ml (0.88 mmol) of a 1M solution of tetrabutylammonium fluoride in THF and 2.765 g (19.44 mmol) of trifluoromethyltrimethylsilane (TMS-CF3), and after chromatography on silica gel, eluting with a 98/2 mixture of dichloromethane and methanol, gives 2.23 g of pure product in the form of a colourless oil.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:12][C:13](=[O:21])[CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)=[C:6]([CH:11]=1)[C:7]([O:9]C)=O.CO[Na]>O1CCCC1.CO>[Br:1][C:2]1[CH:11]=[C:6]2[C:5](=[CH:4][CH:3]=1)[NH:12][C:13](=[O:21])[CH:14]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1)[C:7]2=[O:9]
Reactant: COC(=O)c1cc(Br)ccc1NC(=O)Cc1ccccn1
Agent: CO[Na]
Solvent: CO
Solvent: C1CCOC1
Product: O=C1Nc2ccc(Br)cc2C(=O)C1c1ccccn1
Temperature: 20 °C
Reaction time: 8 h

Procedure:
Into a 250-mL round-bottom flask were placed a solution of methyl 5-bromo-2-[2-(pyridin-2-yl)acetamido]benzoate (3 g, 7.73 mmol, 1.00 equivalent, 90%, Intermediate 61, step a) in tetrahydrofuran (30 mL). A 2.38 M solution of MeONa in MeOH (freshly prepared from dissolving 2.74 g of Na in 50 mL of anhydrous MeOH solution, 11.7 mL, 27.85 mmol, 4.00 equivalents) was then added. The resulting solution was stirred overnight at 20° C., and the precipitate was collected by filtration to give the title compound as a white solid.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH:10]=[CH:9][S:8][C:7]=2[CH:11]=1.[Na].C(S)C>CN(C=O)C>[S:8]1[CH:9]=[CH:10][C:6]2[CH:5]=[CH:4][C:3]([OH:2])=[CH:11][C:7]1=2
Reactant: COc1ccc2ccsc2c1
Agent: [Na]
Solvent: CCS
Solvent: CN(C)C=O
Product: Oc1ccc2ccsc2c1
Temperature: 150 °C
Reaction time: 8 h
Yield: 36.5 %

Procedure:
Dissolve 6-methoxy-benzo[b]thiophene (J. Med. Chem. 32:2548, 1989; 26.1 g, 146 mmol) in DMF (500 mL). Add ethanethiol sodium salt (37 g, 440 mmol) and heat to 150° C. with stirring overnight. Add additional ethanethiol sodium salt (12.8 g, 152 mmol) and continue to heat at 150° C. overnight. Concentrate in vacuo to ¼ volume. Partition reaction mixture between ethyl acetate (500 mL) and water (500 mL), separate layers, wash organic layer with water (2×500 mL), brine (500 mL), and dry with magnesium sulfate. Filter and concentrate in vacuo to give 8 g of benzo[b]thiophen-6-ol. Back extract aqueous layers with ethyl acetate (3×1000 mL) wash organics with brine, and dry with magnesium sulfate. Concentrate in vacuo to obtain an additional 15 grams of benzo[b]thiophen-6-ol. Distill off remaining DMF to yield 22.7 g (100%) of benzo[b]thiophen-6-ol.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.Br[CH2:9][CH2:10][CH2:11][OH:12]>C1(C)C=CC=CC=1>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:9][CH2:10][CH2:11][OH:12])[CH2:4][CH2:3]1
Reactant: CN1CCNCC1
Reactant: OCCCBr
Solvent: Cc1ccccc1
Product: CN1CCN(CCCO)CC1
Temperature: 80 °C
Reaction time: 8 h
Yield: 86 %

Procedure:
1-Methylpiperazine (6.99 mL, 63 mol) was dissolved in toluene (30 mL). 3-Bromopropanol (2.62 mL, 30 mmol) was added slowly and the mixture was stirred overnight. After heating to 80° C. for 2 h and cooling to r.t., the mixture was filtered and the filter cake was washed thoroughly with toluene. After removal of the toluene, the residue was subjected to Kugelrohr distillation (b.p., 180° C./2 mbar) to obtain a colourless oil (4.08 g, 25.8 mmol, 86%). 1H NMR (CDCl3): δ=1.70 (Ψ-quint, J≈5.8 Hz, 2 H), 2.26 (s, 3 H), 2.35-2.6 (m, 8 H), 2.60 (Ψ-t, J=5.8 Hz, 2 H), 3.77 (Ψ-t, J=5.3 Hz, 2 H), 4.09 (s, br., 1 H).
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[CH:19][C:5]2[O:6][C:7]3[CH:18]=[CH:17][CH:16]=[CH:15][C:8]=3[CH2:9][N:10]([C:11]([NH:13][NH2:14])=[O:12])[C:4]=2[CH:3]=1.[C:21](Cl)(=[O:29])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].C(=O)(O)[O-].[Na+]>>[C:21]([NH:14][NH:13][C:11]([N:10]1[CH2:9][C:8]2[CH:15]=[CH:16][CH:17]=[CH:18][C:7]=2[O:6][C:5]2[CH:19]=[CH:20][C:2]([Cl:1])=[CH:3][C:4]1=2)=[O:12])(=[O:29])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: CCCCCCCC(=O)Cl
Reactant: NNC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21
Agent: O=C([O-])O
Agent: [Na+]
Product: CCCCCCCC(=O)NNC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21

Procedure:
The reaction of an alkanoyl halide and the hydrazide is illustrated by contacting 8-chloro-10,11-dihydrodibenz-[b,f][1,4]oxazepine-10-carboxylic acid hydrazide with octanoyl chloride in the presence of sodium bicarbonate to give 1-octanoyl-2-(8-chloro-10,11-dihydrodibenz[b,f][1,4]oxazepine-10-carbonyl)hydrazine.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][C@@H:3]([OH:6])[CH2:2]1.[C:7](Cl)([Cl:9])=[O:8].C1(C)C=CC=CC=1>C(Cl)Cl>[Cl:9][C:7]([O:6][C@@H:3]1[CH2:4][CH2:5][O:1][CH2:2]1)=[O:8]
Reactant: O=C(Cl)Cl
Reactant: O[C@@H]1CCOC1
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: O=C(Cl)O[C@@H]1CCOC1
Temperature: 25 °C
Yield: 85 %

Procedure:
A stirred solution of (R)-tetrahydrofuran-3-ol (7.9 g, 90 mmol) in anhydrous CH2Cl2 (50 mL) under an N2 atmosphere was cooled in an ice bath, and a 20% solution of phosgene in toluene (134 mL, 270 mmol) was slowly added. The reaction was allowed to warm to room temperature overnight, and the solvent was removed under vacuum to afford (R)-tetrahydrofuran-3-yl chloroformate (12.1 g, 85%) as a clear liquid.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([N:18]1[CH2:26][CH:25]([OH:27])[CH2:24][C@H:19]1[C:20]([O:22][CH3:23])=[O:21])([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12]>C(Cl)Cl>[C:11]([N:18]1[CH2:26][C:25](=[O:27])[CH2:24][C@H:19]1[C:20]([O:22][CH3:23])=[O:21])([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12]
Reactant: COC(=O)[C@@H]1CC(O)CN1C(=O)OC(C)(C)C
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CS(C)=O
Product: COC(=O)[C@@H]1CC(=O)CN1C(=O)OC(C)(C)C
Reaction time: 0.5 h
Yield: 81.5 %

Procedure:
A solution of 3.5 mL (40.2 mmol) of oxalyl chloride in 20 mL of CH2Cl2 was cooled in a −78° C. bath and 3.5 mL (49.3 mmol) of dry DMSO was added. After 30 min, a solution of 5.31 g (23 mmol) of N-(BOC)-4-hydroxy-(L)-proline, methyl ester was added. A precipitate developed during the addition. After 30 min at −78° C., 15 mL (107 mmol) of TEA was added. Another 30 mL of CH2Cl2 was added to the reaction mixture to facilitate stirring and cold bath was removed. After 1.5 hr the solution was partitioned between CH2Cl2 and water. The organic layer was washed with water, 1.2 N HCl, brine then dried over anydrous Na2SO4. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel eluted with a gradient of 20-40% EtOAc/hexane to yield N-(BOC)-4-oxo-(L)-proline, methyl ester (4.56 g).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([N+]([O-])=O)[CH:5]=[CH:4][N+:3]=1[O-:11].C([Cl:15])(=O)C.C(=O)([O-])[O-].[Na+].[Na+]>>[Cl:15][C:6]1[CH:5]=[CH:4][N+:3]([O-:11])=[C:2]([CH3:1])[CH:7]=1
Reactant: CC(=O)Cl
Reactant: Cc1cc([N+](=O)[O-])cc[n+]1[O-]
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: Cc1cc(Cl)cc[n+]1[O-]
Temperature: 0 °C
Yield: 32.7 %

Procedure:
15.4 g (0.1 mol) of 2-methyl-4-nitropyridine 1-oxide was added to 78.5 g (1 mol) of acetyl chloride at -10° C. The obtained mixture was stirred under cooling with ice for 0.5 hour. After the completion of the reaction, 300 ml of ice-water was added to the reaction mixture. The obtained mixture was neutralized with sodium carbonate and extracted with chloroform. The extract was dried over magnesium sulfate and filtered. The filtrate was concentrated under a reduced pressure and purified by silica gel column chromatography (ethyl acetate/n-hexane/methanol) to obtain 4.7 g of the title compound.
Reaction SMILES: [Br:1][C:2]1[C:7]([O:8][CH2:9][O:10][CH3:11])=[CH:6][C:5]([O:12][CH2:13][O:14][CH3:15])=[CH:4][C:3]=1[CH2:16][OH:17].[H-].[Na+].[CH3:20]I>C1COCC1.CCOCC>[Br:1][C:2]1[C:3]([CH2:16][O:17][CH3:20])=[CH:4][C:5]([O:12][CH2:13][O:14][CH3:15])=[CH:6][C:7]=1[O:8][CH2:9][O:10][CH3:11]
Reactant: CI
Reactant: COCOc1cc(CO)c(Br)c(OCOC)c1
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: COCOc1cc(COC)c(Br)c(OCOC)c1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 70 %

Procedure:
To a solution of (2-bromo-3,5-bis-methoxymethoxy-phenyl)-methanol (7.68 g, 24.94 mmol) in THF (50 mL) was added NaH at 0° C. The mixture was stirred at room temperature for 20 minutes then MeI (7.84 mL) was added and the resulting mixture was stirred at room temperature for 2 hours. The mixture was diluted with ether (50 mL), filtered through a pad of celite and concentrated in vacuo. The residue was purified by silica gel flash column chromatography to give 2-bromo-1,5-bis-methoxymethoxy-3-methoxymethyl-benzene (5.66 g, 70%). 1H NMR (400 MHz, CDCl3δ 6.90 (s, 1H), 6.80 (s, 1H), 6.77 (s, 1H), 5.25 (s, 2H), 5.20 (s, 2H), 4.50 (s, 23.77 (s, 3H), 3.40 (s, 6H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[OH:12][CH2:13][C@H:14]1[CH2:18][CH2:17][CH2:16][N:15]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20]>N1C=CC=CC=1.C(OCC)(=O)C>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:12][CH2:13][C@H:14]2[CH2:18][CH2:17][CH2:16][N:15]2[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1CO
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OC[C@H]2CCCN2C(=O)OC(C)(C)C)cc1
Reaction time: 2.5 h

Procedure:
4-Methylbenzenesulfonyl chloride (8.83 g, 46.32 mmol) was added to a solution of tert-butyl (2R)-2-(hydroxymethyl)-1-pyrrolidinecarboxylate (5.48 g, 27.24 mmol) in pyridine (25 ml). The reaction mixture was stirred for 2.5 hrs, after which time the reaction was diluted with ethyl acetate (100 ml) and washed with water (100 ml), saturated copper sulphate solution (100 ml), dried over MgSO4 and the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel using ethyl acetate:pentane (20:80) as the eluant to afford the title compound as a clear oil, 9.2 g, (95%).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][C:3]=1[S:12]([C:15]([F:18])([F:17])[F:16])(=[O:14])=[O:13].[N:19]1([CH2:25][CH2:26][C@@H:27]([NH2:36])[CH2:28][S:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[N:19]1([CH2:25][CH2:26][C@@H:27]([NH:36][C:2]2[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][C:3]=2[S:12]([C:15]([F:18])([F:17])[F:16])(=[O:14])=[O:13])[CH2:28][S:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:20][CH2:21][O:22][CH2:23][CH2:24]1
Reactant: NS(=O)(=O)c1ccc(F)c(S(=O)(=O)C(F)(F)F)c1
Reactant: N[C@H](CCN1CCOCC1)CSc1ccccc1
Product: NS(=O)(=O)c1ccc(N[C@H](CCN2CCOCC2)CSc2ccccc2)c(S(=O)(=O)C(F)(F)F)c1

Procedure:
reacting 4-fluoro-3-((trifluoromethyl)sulfonyl)benzenesulfonamide, (1R)-3-morpholin-4-yl-1-((phenylthio)methyl)propylamine and a sixth base to provide 4-(((1R)-3-morpholin-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide and isolating or not isolating the 4-(((1R)-3-morpholin-4-yl-1-((phenylthio)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide.
Reaction SMILES: [OH:1][CH:2]1[C:11]2[N:10]=[CH:9][CH:8]=[CH:7][C:6]=2[CH2:5][CH2:4][CH2:3]1>C(Cl)Cl.[O-2].[O-2].[Mn+4]>[N:10]1[C:11]2[C:2](=[O:1])[CH2:3][CH2:4][CH2:5][C:6]=2[CH:7]=[CH:8][CH:9]=1
Reactant: OC1CCCc2cccnc21
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Product: O=C1CCCc2cccnc21
Reaction time: 18 h
Yield: 81.8 %

Procedure:
To a stirred solution of 8-hydroxy-5,6,7,8-tetrahydroquinoline (13.96 g, 93.6 mmol) in dry CH2Cl2 (400 mL) was added activated manganese dioxide (85% purity, 82.22 g, 804 mmol). The resulting heterogeneous mixture was stirred 18 h, at which point the black slurry was filtered through a cake of celite and washed with CH2Cl2 (3×50 mL). The combined washings were concentrated to afford 11.27 g (82%) of the title compound as a pale yellow solid, which was used in subsequent reactions without further purification. 1H NMR (CDCl3) δ 2.17-2.25 (m, 2H), 2.82 (t, 2H, J=7 Hz), 3.04 (t, 2H, J=6 Hz), 7.37 (dd, 1H, J=9, 6 Hz), 7.66 (dd, 1H, J=9, 1 Hz), 8.71 (dd, 1H, J=6, 1 Hz); 13C NMR (CDCl3) δ 22.2, 28.6, 39.2, 126.6, 137.3, 140.5, 147.6, 148.6, 196.5. ES-MS m/z 148 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]([O:19][CH3:20])([C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:17][CH3:18])[CH:13]=2)[CH:8]=1)[CH:4]([OH:6])[CH3:5].[C:21]1([CH3:31])[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1>N1C=CC=CC=1>[C:21]1([CH3:31])[CH:26]=[CH:25][C:24]([S:27]([O:6][CH:4]([CH3:5])[C:3]([O:19][CH3:20])([O:2][CH3:1])[C:7]2[CH:16]=[CH:15][C:14]3[C:9](=[CH:10][CH:11]=[C:12]([O:17][CH3:18])[CH:13]=3)[CH:8]=2)(=[O:29])=[O:28])=[CH:23][CH:22]=1
Reactant: COc1ccc2cc(C(OC)(OC)C(C)O)ccc2c1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Product: COc1ccc2cc(C(OC)(OC)C(C)OS(=O)(=O)c3ccc(C)cc3)ccc2c1
Temperature: 10 °C
Reaction time: 8 h

Procedure:
The oil, 1,1-dimethoxy-1-(6-methoxy-2-naphthyl) propan-2-ol, prepared in Example 29 is dissolved in 60 ml of pyridine and cooled to 10° C. Then 13 g of p-toluenesulfonyl chloride is added and the reaction mixture is stirred to dissolve the p-toluenesulfonyl chloride. The reaction mixture is allowed to stand overnight and the precipitation of pyridine hydrochloride is observed. The reaction mixture is poured into 7 volumes of water and extracted with ethyl ether. The ethereal layer is washed with dilute hydrochloric acid and then with dilute sodium hydroxide. The ethereal extract is dried over magnesium sulfate and evaporated to yield 1,1-dimethoxy-1-(6-methoxy-2-naphthyl)prop-2-yl p-toluenesulfonate, as an oil, [which is characterized by an NMR spectra in duterochloroform of τ=8.86 (doublet, J=2.5), 7.57, 6.82, 6.74, 6.09, 4.87 (quartet, J=2.5), 2.2-3.0 (multiplet)].
Reaction SMILES: CS(O[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]/[CH:14]=[CH:15]\[CH2:16]/[CH:17]=[CH:18]\[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])(=O)=O.[Br-:24].[Mg+2].[Br-].O>CCOCC>[CH2:6]([Br:24])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]/[CH:14]=[CH:15]\[CH2:16]/[CH:17]=[CH:18]\[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: CCCCC/C=C\C/C=C\CCCCCCCCOS(C)(=O)=O
Reactant: [Br-]
Agent: [Mg+2]
Solvent: CCOCC
Solvent: O
Product: CCCCC/C=C\C/C=C\CCCCCCCCBr
Reaction time: 21 h
Yield: 109.6 %

Procedure:
A mixture of linoleyl methane sulfonate (6.2 g, 18 mmol) and magnesium bromide etherate (17 g, 55 mmol) in anhydrous ether (300 mL) was stirred under argon overnight (21 hours). The resulting suspension was poured into 300 mL of chilled water. Upon shaking, the organic phase was separated. The aqueous phase was extracted with ether (2×150 mL). The combined ether phase was washed with water (2×150 mL), brine (150 mL), and dried over anhydrous Na2SO4. The solvent was evaporated to afford 6.5 g of colourless oil. The crude product was purified by column chromatography on silica gel (230-400 mesh, 300 mL) and eluted with hexanes. This gave 6.2 g (approximately 100%) of linoleyl bromide (II). 1H NMR (400 MHz, CDCl3) δ: 5.27-5.45 (4H, m, 2×CH═CH), 3.42 (2H, t, CH2Br), 2.79 (2H, t, C═C—CH2-C═C), 2.06 (4H, q, 2× allylic CH2), 1.87 (2H, quintet, CH2), 1.2-1.5 (16H, m), 0.90 (3H, t, CH3) ppm.
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:9]([SH:13])[CH2:10][CH2:11][SH:12].B(F)(F)F.CCOCC>C(Cl)Cl>[C:2]1([CH:1]2[S:13][CH2:9][CH2:10][CH2:11][S:12]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: SCCCS
Reactant: O=Cc1ccccc1
Agent: FB(F)F
Solvent: CCOCC
Solvent: ClCCl
Product: c1ccc(C2SCCCS2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 87 %

Procedure:
To a solution of benzaldehyde (10.6 g, 100 mmol) and 1,3-propane dithiol in CH2Cl2 (150 mL) at room temperature was dropwise added BF3.Et2O (6.3 mL, 50 mmol) and the resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was then diluted with CH2Cl2, filtered and the filtrate washed with brine, saturated NaHCO3, brine and dried over Na2SO4. The solvent was removed under reduced pressure to afford a white solid, which was recrystallized from a 1:1 mixture of ether and hexane to afford 17.0 g (87%) of the title compound (65) as white crystalline needles. 1H NMR (CDCl3, 400 MHz): δ 1.91 (m, 1H), 2.14 (m, 1H), 2.89 (m, 2H), 3.04 (m, 2H), 5.16 (s, 1H), 7.35-7.28 (m, 3H), 7.46 (m, 2H).