3-benzyl-[1,2]oxathiolane 2,2-dioxide

Preparation of 4-{[(1S)-1-(4-fluorophenyl)ethyl]amino}-1-phenyl-2-butanesulfonic acid Preparation of 4-amino-1-phenyl-2-butanesulfonic acid (Compound QQ); To a -78 C. solution of 1, 3-propane sultone (1 eq) in anhydrous tetrahydrofuran (THF, 1.8M) was added butyl lithium (2.5 M in hexanes, 1.5 eq). The solution was stirred at -78 C. for 30 minutes before benzyl bromide (1 eq diluted with THF) was added via syringe pump over a 30 minute period. The reaction mixture was stirred at -78 C. for 2 hours. The reaction mixture was warmed up to 0 C. before water (100 mL) was slowly added. The organic layer was recovered and diluted with EtOAc (20 mL). The solution was dried with Na2SO4, filtered and evaporated under reduced pressure. The product was purified on a silica gel pad (90% Hex/EtOAc to 60% Hex/EtOAc) affording the corresponding 1-Benzyl-1, 3-propane sultone. To 0 C. ammonium hydroxide (28-30% NH3, 50 eq) was added via syringe pump over a 4 hours period a solution of 1-Benzyl-1, 3-propane sultone (1 eq) in tetrahydrofuran (0.8 M). The solution was stirred at 0 C. for an additional 30 minutes. The solvent was co-evaporated with EtOH. The solid was suspended in EtOH. The mixture was stirred at reflux for 1 hour. After cooling to room temperature, the solid material was collected by filtration, washed with EtOH (2×20 mL) and dried in a vacuum oven (50 C.), affording the title compound (57%). 1H NMR (500 MHz, D2O) delta (ppm) 1.77 (m, 1H), 1.89 (m, 1H), 2.57 (t, 1H, J=10.5 Hz), 2.76 (m, 1H), 2.94 (m, 1H), 3.05 (m, 1H), 3.23 (dd, 1H, J=4.1 Hz, 13.9 Hz), 7.22 (m, 5H); 13C NMR (125 MHz, D2O) delta (ppm) 26.89, 36.05, 37.79, 59.42, 127.12, 129.03, 129.48, 138.16; ES-MS 230 (M+H).Preparation of 4-(tert-butylamino)-1-phenyl-2-butanesulfonic acid (Compound QN); To a -78 C. solution of 1, 3-propane sultone (1 eq) in anhydrous tetrahydrofuran (THF, 1.8 M) was added butyl lithium (2.5 M in hexanes, 1.5 eq). The solution was stirred at -78 C. for 0.5 hours before benzyl bromide (1 eq diluted with THF) was added via syringe pump over 0.5 hours period. The reaction mixture was stirred at -78 C. for 2 hours. The reaction mixture was warmed up to 0 C. before water (100 mL) was slowly added. The organic layer was recovered and diluted with EtOAc (20 mL). The solution was dried with Na2SO4, filtered and evaporated under reduced pressure. The product was purified on a silica gel pad (90% Hex/EtOAc to 60% Hex/EtOAc) affording the resulting 1-Benzyl-1, 3-propane sultone. To a solution of 1-Benzyl-1, 3-propane sultone (1 eq) in 25% Toluene/Acetonitrile (0.8 M) was added Tert-Butylamine (1.05 eq). The solution was stirred at reflux for 4 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration and washed with acetone (2×20 mL). The solid material was suspended in EtOH. The suspension was stirred at reflux for 1 hour. The mixture was cooled to room temperature, the solid material was collected by filtration, washed with acetone (2×20 mL) and dried in a vacuum oven (50 C.), affording the title compound. 1H NMR (D2O, 500 MHz) delta ppm 7.23 (m, 5H), 3.28 (dd, 1H, J=3.7 Hz, 13.9 Hz), 3.06 (m, 1H), 2.87 (m, 1H), 2.58 (m, 2H), 1.90 (m, 1H), 1.76 (m, 1H), 1.06 (s. 9H). 13C (D2O, 125 MHz) delta ppm 138.09, 129.45, 129.13, 127.25, 59.41, 57.09, 39.49, 36.11, 26.40, 24.90. ES-MS 284 (M-1).To a solution of (S)-(-)-1-(4-fluorophenyl)ethylamine (1.0 g, 7.2 mmol) in cosolvent of toluene and acetonitrile (10 mL, v/v=1:3) was added a solution of Preparation of 4-{[(1S)-1-(4-fluorophenyl)ethyl]amino}-1-phenyl-2-butanesulfonic acid To a -78 C. solution of 1, 3-propane sultone (5.0 g, 41 mmol) in anhydrous THF (150 mL) was added butyl lithium (2.5 M in hexanes, 18 mL, 41 mmol). The solution was stirred at -78 C. for 0.5 hour before benzyl bromide (4.9 mL, 41 mmol) was added via syringe pump over 0.5 hour period. The reaction mixture was stirred at -78 C. for 2 hours. The reaction mixture was warmed up to 0 C. before water (100 mL) was slowly added. The organic layer was recovered. The aqueous phase was extracted EtOAc (2*25 mL). The organic extracts were combined, dried over Na2SO4, filtered and evaporated under reduced pressure. The product was purified by flash chromatography (Rf=0.14, 80% Hex/EtOAc) affording the corresponding

Molecular Weight:212.27
XLogP3:1.8
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:212.05071541
Monoisotopic Mass:212.05071541
Topological Polar Surface Area:51.8
Heavy Atom Count:14
Complexity:272
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes