Sodium hydride → HCID 118468052, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methylthiazolidin-2-one (50 mg, 0.152 mmol) in THF (1 ml) was added NaH (7.59 mg, 0.190 mmol) at −20° C. 30 Minutes later, a solution of 2-bromo-5-(trifluoromethyl)benzyl methanesulfonate (50.6 mg, 0.152 mmol) in THF (0.5 ml) was added. Stirring of the reaction continued for 1 hour. A crude NMR spectrum showed only 25% product formation. The reaction temperature was increased to −10° C., and stirring was continued for another 1 h. The reaction mixture was left in the freezer under N2 atmosphere overnight. NMR and LCMS indicated around a 65% conversion to the desired isomer, with no undesired epimerized product. The reaction was cooled to −10° C., and additional NaH (2.429 mg, 0.061 mmol) was added. Stirring of the reaction mixture was continued for 20 minutes. 2-Bromo-5-(trifluoromethyl)benzyl methanesulfonate (20.2 mg, 0.061 mmol) was added, and the reaction was continued for another 2 hours at −10° C. The reaction mixture was quenched with ice water, and the mixture was diluted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by PTLC by using 35% EtOAc in hexane. 1H NMR (500 MHz, CDCl3): δ 7.90 (s, 1H); 7.85 (s, 2H); 7.76 (d, J=8.3 Hz, 1H); 7.59 (s, 1H); 7.48 (d, J=8.5 Hz, 1H); 5.15 (d, J=7.0 Hz, 1H); 5.02 (d, J=16.0 Hz, 1H); 4.45 (d, J=16.0 Hz, 1H); 4.10-4.11 (m, 1H); 0.97 (d, J=6.5 Hz, 3H).

Provenance & Evidence