3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → 3-(2-Chloro-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-ylmethylene)azetidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

To a suspension of (2-chloro-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-ylmethyl)phosphonic acid dimethyl ester (3.0 g, 7.94 mmol) in THF (150 mL) at −78° C. was added LiHMDS (8.8 mL, 8.80 mmol, 1M solution in THF) and the resulting mixture stirred for 30 min then warmed to r.t. before the addition of a solution of 3-oxo-azetidine-1-carboxylic acid tert-butyl ester (1.51 g, 8.82 mmol) in THF (20 mL). The reaction mixture was stirred at r.t. for 16 h then quenched with H2O and MeOH and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:DCM, 5-100%) affording the title compound as a yellow solid (2.14 g, 63%). LCMS (method A): RT 3.97 min [M+H]+ 423.3

Provenance & Evidence