tert-Butyl bromoacetate → tert-Butyl ((6S,8R)-6-(anilinocarbonyl)-8-methyl-4-oxo-3-{[3-(trifluoromethyl)benzyl]amino}-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidin-8-yl)acetate

Participants

Reaction Conditions

Reaction Steps

To a solution of 12c (0.987 g, 1.71 mmol) in 8.6 mL THF at −78° C., was added LiHMDS (1M in THF, 3.59 mL, 3.59 mmol). The red solution was stirred at −78° C. for 10 min, then a solution of t-butyl bromoacetate (0.278 mL, 1.88 mmol) was added. The reaction was allowed to slowly warm to −50° C. over 1 h, then was quenched with the addition of sat. NH4Cl. The mixture was poured into 50 mL H2O and extracted with 100 mL EtOAc. The organic phase was washed with 0.1N HCl and brine, dried (Na2SO4), and concentrated. The product was purified by flash chromatography (50% EtOAc/hexanes) to afford 432 mg (37%) of 92a. 1H NMR (300 MHz, CDCl3) δ8.94 (br s, 1H), 7.51-7.26 (m, 15H), 7.09 (t, J=7.5, 1H), 5.25-5.13 (m, 3H), 5.06 (dd, J=9.4, 6.0, 1H), 4.85 (br s, 2H), 2.89 (dd, J=13.9, 5.8, 1H), 2.80 (ABq, JAB=16.8, δνAB=91.9, 2H), 2.44 (dd, J=13.5, 9.1, 1H), 1.38 (s, 12H); MS (ESI) 713.2 (M+Na+), 689.4 (M−H+).

Provenance & Evidence