tert-Butanol → {4-[1-(4-pentafluoroethyloxyphenyl)-1H-[1,2,4]triazol-3-yl]-phenyl}-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 4-[1-(4-pentafluoroethyloxyphenyl)-1H-[1,2,4]triazol-3-yl]-phenylamine (1.0 g, 2.7 mmol) in dry THF (8 mL) was stirred while p-nitrophenyl chloroformate (0.60 g, 3 mmol) was added in one portion and the solution was allowed to stir for 3 h. The resulting solid was filtered and air-dried. A smaller portion of the p-nitrophenylcarbamate (152 mg, 0.28 mmol) was suspended in dry THF (3 mL). To this were added 2-methyl-2-propanol (41 mg, 0.32 mmol) in dry THF (1 mL) followed by NaH (60% mineral oil dispersion; 26 mg, 0.67 mmol) in one portion. Additional dry THF (1 mL) was used to rinse joints, etc. The solution was heated to 60° C. (external) for 1.5 h, at which point TLC (3:3:3:1 EtOAc/hexanes/CH2Cl2/acetone) showed no starting material. The mixture was cooled and allowed to stir at 25° C. for 20 h. The mixture was cooled, poured on to ice-water (50 mL), and extracted with EtOAc (3×50 mL). The combined extracts were washed with satd aq NaCl (75 mL), dried (Na2SO4), filtered and concentrated. RP-HPLC (acid-free medium water-acetonitrile gradient) provided the title compound (31 mg, 23%) as an off-white solid: mp 205-209° C.; 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 8.12 (d, J=9.0 Hz, 2H), 7.80 (d, J=9.3 Hz, 2H), 7.48 (d, J=8.8 Hz, 2H), 7.38 (d, J=9.0 Hz, 2H), 6.58 (s, 1H), 1.54 (s, 9H); ESIMS m/z 471 (M+H), 469 (M−H). Compound 2 in Table 1 was synthesized as in Example 56.

Provenance & Evidence