Methyl chloroformate → HCID 58169881, compound

Participants

Reaction Steps

To a solution of phenylmethyl(5S,7R)-8-{[{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}(methyl)amino]carbonyl}-7-(4-fluoro-2-methylphenyl)-2-oxo-1,8-diazaspiro[4.5]decane-1-carboxylate (Intermediate 33, 85 mg) in Tetrahydrofuran (THF) (2 ml), at −78° C., LiHMDS (0.257 ml, 0.257 mmol) was added and left stirring at this temperature for 1 hr. methyl chloroformate (0.019 ml, 0.245 mmol) was added at the same temperature and the reaction was left at this temperature for 2 hrs. To the solution was added NH4Cl saturated solution, followed by DCM and water. The two phases were separated and the aqueous one was extracted with DCM. The combined organic layers were filtered through a phase separator tube and the solvent was removed in vacuo obtaining the title compound (83 mg) as a white foam. This batch was used in the next step without further purification. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.01 (s, 1H) 7.67 (s, 2H) 7.24-7.48 (m, 5H) 6.85-7.00 (m, 2H) 6.70-6.84 (m, 1H) 5.09-5.29 (m, 3H) 4.34 (d, 1 H) 3.99 (t, 1H) 3.70 (s, 3H) 2.65 (s, 3H) 2.58-3.44 (m, 2H) 2.34 (s, 3H) 1.54-2.45 (m, 6H) 1.47 (d, 3H); Mixture of two diastereoisomers ratio ˜50:50 (for example visible on the signal of CH(6) see annotation in the spectrum). The atom numbering shown in the following structure is included for the purpose of correlation with the NMR data only.

Provenance & Evidence