Hydrochloric Acid → (S)-N-Cyclohexyl-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-N-(2,2,2-trifluoroethyl)benzamide

Temperature

80 °C

To a solution of (S)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzoic acid (0.10 g, 0.43 mmol), pyridine (0.069, 0.86 mmol), and THF (1 mL) was added SOCl2 (0.046 mL, 0.64 mmol). The reaction was stirred at 80° C. for 2 h. After cooling to room temperature, half of the acid chloride was sequestered for reaction. To this material was added 2 equiv. of N-(2,2,2-trifluoroethyl)cyclohexylamine (0.077 mg, 0.43 mmol). The amide forming reaction was stirred at room temperature overnight. The reaction mixture was poured into water (5 mL), acidified with 5 N HCl and extracted with CH2Cl2 (2 mL). The organic extracts were washed with 1 N NaOH (4 mL), dried with Na2SO4, and removed in vacuo. Silica gel chromatography (gradient 20 to 30% ethyl acetate in hexanes) afforded 21 mg of (S)-N-cyclohexyl-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-N-(2,2,2-trifluoroethyl)benzamide. 1H NMR (400 MHz, CDCl3) δ 1.10-1.20 (m, 3H), 1.42-1.65 (m, 3H), 1.74-1.85 (m, 7H), 2.68 (bs, 1H), 3.68 (bs, 1H), 4.02-4.19 (m, 2 H), 7.44 (d, J=8 Hz, 2H), 7.66 (d, J=8 Hz, 2H).

1. temperatureAfter cooling to room temperature
2. stirringwas stirred at room temperature overnight
3. extractionextracted with CH2Cl2 (2 mL)
4. washThe organic extracts were washed with 1 N NaOH (4 mL)
5. dry with materialdried with Na2SO4
6. customremoved in vacuo

ORD record

ord-2765ad7cd41d40959abdb0c2714e047e

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08637576B2