Diisopropylamine → 3-Hydroxy-3-(2-methylsulfanyl-pyrimidin-4-yl)-propionic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a cold (0° C.) solution of diisopropylamine (5.7 mL, 40.5 mmol) in THF (130 mL) is added dropwise n-butyllithium (16.2 mL of a 2.5 M solution in hexanes, 40.5 mmol). The mixture is stirred for 45 min at 0° C., then the solution is cooled to −78° C. tert-Butyl acetate (5.5 mL, 40.5 mmol) is added dropwise to the reaction mixture. After stirring 40 min at −78° C., a solution of 2-methylsulfanyl-pyrimidine-4-carbaldehyde (5.0 g, 32.4 mmol) is added dropwise. After 30 min at −78° C., the solution is poured into aqueous saturated NH4Cl. The aqueous phase is extracted with EtOAc. The organic phase is dried (MgSO4), filtered and concentrated in vacuo. The crude residue is purified over silica (5% EtOAc/hexanes, followed by 20% EtOAc/hexanes) to afford 7.2 g (82% yield) of the desired product. 1H NMR (300 MHz, CDCl3) δ 8.52 (d, J=5.1 Hz, 1H), 7.22 (d, J=5.1 Hz, 1H), 5.00 (dd, J=8.4, 3.6 Hz, 1H), 2.93 (dd, J=16.5, 3.6 Hz, 1H), 2.70 (dd, J=16.5, 7.8 Hz, 1H), 2.58 (s, 3H), 1.46 (s, 9H); ESI+ MS: m/z (rel intensity) 271.1 (85, M++H).

Provenance & Evidence