Sodium Bicarbonate → {4-[2-(4-trifluoromethylphenyl)-pyrimidin-4-yl]-phenyl}-carbamic acid (2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester

Participants

Reaction Steps

To a mixture cooled in an ice bath of 126 mg (0.40 mmol) of 4-[2-(4-trifluoromethylphenyl)-pyrimidin-4-yl]-phenylamine in 1 mL of dry toluene was added dropwise via syringe 1.6 mL (0.80 mmol) of a 0.5 M solution of potassium hexamethyldisilazide in toluene over a 10-15 minute period. To this mixture was then added dropwise a solution of 148 mg (0.400 mmol) of carbonic acid 4-nitrophenyl ester 3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester in 2 mL of toluene. The contents were allowed to gradually warm to room temperature and stir overnight and were added to cold saturated sodium bicarbonate. The mixture was extracted two times with chloroform and the combined extracts were dried (MgSO4). Concentration gave 130 mg which was purified by chromatography on silica gel using 9:1 DCM/EtOAc to afford 64 mg (29%) of Compound 232. 1HNMR (300 MHz, CDCl3) δ 8.87 (d, J=5.2 Hz, 1H), 8.71 (d, J=8.2 Hz, 2H), 8.26 (d, J=8.8 Hz, 2H), 7.79 (d, J=8.2 Hz, 2H), 7.65 (d, J=5.2 Hz, 1H), 7.63 (d, 2H), 6.86 (br s, 1H), 6.26 (d, J=1.9 Hz, 1H), 3.74-3.70 (m, 2H), 3.61 (s, 3H), 3.60 (s, 3H), 3.57 (s, 3H), 3.53 (m, 1H), 3.24 (t, J=9.5 Hz, 1H), 1.36 (d, J=6.0 Hz, 3H); MS (API-ES+) 549 ([M+H]+, 10), 358 (100); mp 176-179° C.

Provenance & Evidence