4-[(4-bromophenyl)methyl]thiomorpholine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-(4-bromobenzyl)-thiomorpholine (0.20 g, 0.735 mmol) was dissolved in DCM (10 mL) under a nitrogen atmosphere and m-chloroperbenzoic acid (0.13 g, 0.74 mmol) was added portionwise. The reaction mixture was stirred at room temperature for 1 h then purified by flash chromatography (silica, Biotage 50 g column, 0-75% (10% methanol in DCM)) to afford the title compound (0.125 g, 59%). 1H NMR (DMSO-D6, 400 MHz): 7.55-7.49 (m, 2H), 7.31-7.25 (m, 2H), 3.53 (s, 2H), 2.92-2.80 (m, 4H), 2.78-2.65 (m, 2H), 2.64-2.54 (m, 2H). LCMS (Method G): RT=2.66 min, M+H+=289. then purified by flash chromatography (silica, Biotage 50 g column, 0-75% (10% methanol in DCM))

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromobenzyl bromide (1.0 g, 4.0 mmol), triethylamine (0.84 mL, 6.0 mmol) and thiomorpholine (0.82 mL, 8.0 mmol) in THF (10 mL) was stirred at ambient temperature for 16 h. The solvent was evaporated and the resultant residue diluted with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate (2×50 mL). The combined organic layer was dried over sodium sulfate, filtered and evaporated to afford the title compound as an off-white solid (1.13 g, quantitative yield). 1H NMR (CDCl3, 300 MHz): 7.46-7.40 (m, 2H), 7.21-7.16 (m, 2H), 3.45 (s, 2H), 3.15-3.09 (m, 1H), 2.76-2.60 (m, 6H), 2.62-2.57 (m, 1H). The solvent was evaporated the resultant residue diluted with saturated aqueous sodium bicarbonate solution extracted with ethyl acetate (2×50 mL) The combined organic layer was dried over sodium sulfate filtered evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-bromo-4-(bromomethyl)benzene (760 mg) in dry THF (10 ml) containing potassium carbonate (386 mg) was treated dropwise with thiomorpholine (0.36 ml, 369 mg). The resulting mixture was stirred at room temperature under nitrogen for 20 h before filtering and concentrating in vacuo to give impure title compound which was purified by FCC eluting with dichloromethane to give the title compound as a crystalline white solid (634 mg). m.p. 74°-75° C. before filtering concentrating in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-(4-bromobenzyl)-thiomorpholine (0.20 g, 0.735 mmol) was dissolved in DCM (10 mL) under a nitrogen atmosphere and m-chloroperbenzoic acid (0.13 g, 0.74 mmol) was added portionwise. The reaction mixture was stirred at room temperature for 1 h then purified by flash chromatography (silica, Biotage 50 g column, 0-75% (10% methanol in DCM)) to afford the title compound (0.125 g, 59%). 1H NMR (DMSO-D6, 400 MHz): 7.55-7.49 (m, 2H), 7.31-7.25 (m, 2H), 3.53 (s, 2H), 2.92-2.80 (m, 4H), 2.78-2.65 (m, 2H), 2.64-2.54 (m, 2H). LCMS (Method G): RT=2.66 min, M+H+=289. then purified by flash chromatography (silica, Biotage 50 g column, 0-75% (10% methanol in DCM))

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromobenzyl bromide (1.0 g, 4.0 mmol), triethylamine (0.84 mL, 6.0 mmol) and thiomorpholine (0.82 mL, 8.0 mmol) in THF (10 mL) was stirred at ambient temperature for 16 h. The solvent was evaporated and the resultant residue diluted with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate (2×50 mL). The combined organic layer was dried over sodium sulfate, filtered and evaporated to afford the title compound as an off-white solid (1.13 g, quantitative yield). 1H NMR (CDCl3, 300 MHz): 7.46-7.40 (m, 2H), 7.21-7.16 (m, 2H), 3.45 (s, 2H), 3.15-3.09 (m, 1H), 2.76-2.60 (m, 6H), 2.62-2.57 (m, 1H). The solvent was evaporated the resultant residue diluted with saturated aqueous sodium bicarbonate solution extracted with ethyl acetate (2×50 mL) The combined organic layer was dried over sodium sulfate filtered evaporated