Reaction #325909

Reaction equation

(R)—N-((3-Fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)(4-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide

Benzylmagnesium chloride

→

(R)—N—((S)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide

Solvents

CH2Cl2

Conditions

Workup

1. 1
   workup.ADDITIONBF3Et2O (0.10 mL, 2.0 eq) was added dropwise
2. 2
   workup.STIRRINGthe resulting mixture was stirred at −78° C. for 1.5 h
3. 3
   OtherThe reaction mixture was quenched with sat. NH4Cl
4. 4
   Extractionextracted with Et2O (2×)
5. 5
   WashThe combined organic portion was washed with H2O and brine
6. 6
   Dryingdried over Na2SO4
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated to dryness
9. 9
   OtherThe residue was purified by flash chromatography (silica gel, EtOAc/hexanes=0-30%)

Procedure

(R)—N-((3-Fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)(4-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (150 mg, 0.34 mmol) was stirred in anhydrous CH2Cl2 (7 mL) at −78° C. for 5 min under Argon. BF3Et2O (0.10 mL, 2.0 eq) was added dropwise. The mixture was stirred at −78° C. for 10 min. Benzylmagnesium chloride (1.0 M in Et2O, 1.4 mL, 3.0 eq) was added slowly at −78° C., and the resulting mixture was stirred at −78° C. for 1.5 h. The reaction mixture was quenched with sat. NH4Cl and then extracted with Et2O (2×). The combined organic portion was washed with H2O and brine, dried over Na2SO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography (silica gel, EtOAc/hexanes=0-30%) to give the fast eluting fraction corresponding to (R)—N—((S)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide (29 mg): 1H NMR (400 MHz, CDCl3) δ ppm 1.23 (s, 9H) 3.63 (d, J=12.4 Hz, 1H), 3.94 (d, J=12.4 Hz, 1H), 4.21 (s, 1H), 6.90 (m, 1H), 5.90 (m, 1H), 6.94-7.09 (m, 4H), 7.16-7.20 (m, 4H), 7.31-7.39 (m, 2H); LC-MS (ESI) 530.36 (M+H), retention time=4.11 min (10-90% MeOH in H2O with 0.1% TFA in a 4-min run); and the slow eluting fraction corresponding to (R)—N—((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide (146 mg, total yield: 96.4%): 1H NMR (400 MHz, CDCl3) δ ppm 7.35-7.43 (m, 2H), 7.13-7.20 (m, 3H), 7.07 (t, J=8.72 Hz, 2H), 6.93 (dd, J=7.58, 1.77 Hz, 2H), 6.84 (d, J=8.59 Hz, 1H), 6.70 (m, 2H), 5.85 (tt, J=52, 4 Hz, 1H), 4.25 (s, 1H), 4.02 (d, J=12.63 Hz, 1H), 3.58 (d, J=12.63 Hz, 1H), 1.20 (s, 9H); 13C NMR (CDCl3) δ ppm 23.02, 46.99, 56.53, 65.70, 104.55, 104.96, 105.37, 107.06, 107.47, 107.92, 108.17, 109.56, 109.97, 112.32, 112.55, 115.37, 115.58, 116.13, 116.41, 116.69, 119.12, 127.21, 128.14, 130.91, 130.99, 132.07, 134.34, 137.48, 137.51, 149.09, 149.21, 150.52, 150.45, 161.20, 163.67; LC-MS (ESI) 530.36 (M+H), retention time=4.11 min (10-90% MeOH in H2O with 0.1% TFA in a 4-min run).

Source