(NE,R)-2-methyl-N-[[4-(trifluoromethyl)pyridin-2-yl]methylidene]propane-2-sulfinamide → (R)-2-methyl-propane-2-sulfinic acid [(R)-1-(4-trifluoromethyl-pyridin-2-yl)-ethyl]-amide

Temperature

-78 °C

To a solution of (R)-2-methyl-propane-2-sulfinic acid 1-(4-trifluoromethyl-pyridin-2-yl)-meth-(E)-ylideneamide (0.34 g, 1.22 mmol) in THF (5 mL) at −78° C. was slowly added methylmagnesium bromide (3.0 M in Et2O) (0.73 mL, 2.2 mmol). The reaction mixture was stirred at −78° C. for 30 min then quenched cold with saturated aqueous NH4Cl. The mixture was warmed to room temperature, diluted with water, and extracted with EtOAc (2×). the combined organics were dried over MgSO4 and concentrated. NMR analysis showed an approx 8:1 mixture of diastereomers. The residue was purified by chromatography with 50% to 100% EtOAc/hexanes to afford 225 mg (63%) of (R)-2-methyl-propane-2-sulfinic acid [(R)-1-(4-trifluoromethyl-pyridin-2-yl)-ethyl]-amide as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.75 (d, J=5.3 Hz, 1H), 7.51 (s, 1H), 7.42 (d, J=5.3 Hz, 1H), 4.77 (d, J=4.9 Hz, 1H), 4.67 (quin, J=6.3 Hz, 1H), 1.55 (d, J=6.8 Hz, 3H), 1.27 (s, 9H). The single diastereomer obtained was assigned as RSR based on literature precedent (Kuduk, et. al. Tetrahedron Lett. 2004, 45, 6641).

1. customat −78° C.
2. customthen quenched cold with saturated aqueous NH4Cl
3. temperatureThe mixture was warmed to room temperature
4. additiondiluted with water
5. extractionextracted with EtOAc (2×)
6. dry with materialthe combined organics were dried over MgSO4
7. concentrationconcentrated
8. additionan approx 8:1 mixture of diastereomers
9. customThe residue was purified by chromatography with 50% to 100% EtOAc/hexanes

ORD record

ord-0c8e1691e37d4f9a97fe6183144e9b3f

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2