Diisopropylamine → 2-[5-(3-Amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,1,1-trifluoropropan-2-ol

Participants

Reaction Conditions

Reaction Steps

To diisopropylamine (18.73 ml, 131 mmol) in THF (263 mL) at −78° C. was added n-butyllithium (2.5 M in hexanes, 54.7 ml, 137 mmol). The reaction was aged for 30 minutes at −40° C. before cooling to −78° C. Intermediate 16 (10 g, 52.6 mmol) was added as a solution in 5 mL THF at −78° C. and was then warmed to 0° C. over 2 hours. The reaction was once again cooled to −78° C. before adding 1,1,1-trifluoroacetone (14.85 mL, 158 mmol) as a solution in 5 mL THF at −78° C. The reaction was allowed to warm to room temperature slowly, and was diluted with water and DCM. The layers were separated and the organic layer was dried over sodium sulfate and was concentrated in vacuo. The resultant residue was purified on silica gel (0-30% ethyl acetate in hexanes) to yield a yellow oil which solidified in hexanes overnight. The yellow to off-white solid was sonicated and filtered to yield 2-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,1,1-trifluoropropan-2-ol (11.69 g, 38.7 mmol, 73.6%). MS APCI: [M+H]+ m/z 303.0. 1H NMR (500 MHz, CDCl3) δ 7.85 (s, 1H), 6.76 (s, 1H), 6.67 (s, 1H), 6.52 (s, 1H), 4.53 (br s, 2H), 2.29 (s, 3H), 1.83 (s, 3H).

Provenance & Evidence