Imidazole → (S)-methyl 2-(tert-butyldimethylsilyloxy)-3-ethoxypropanoate

A solution of tert-butylchlorodimethylsilane (17.71 g, 117.52 mmol) in dry DMF (50 mL) was added dropwise to a stirred solution of (S)-methyl 2-hydroxy-3-ethoxypropanoate (14.51 g, 97.94 mmol) and 1H-imidazole (13.33 g, 195.87 mmol) in dry DMF (70 mL) at 20° C., over a period of 2 minutes. The resulting solution was stirred at ambient temperature for 20 hours. The reaction mixture was concentrated and diluted with EtOAc (500 mL), washed sequentially with water (4×100 mL) and saturated brine (100 mL). The organic layer was dried (MgSO4) and evaporated. The residue was purified by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane to afford methyl (2S)-2-(tert-butyl-dimethylsilyl)oxy-3-ethoxypropanoate (14.8 g, 57%). 1H NMR (400 MHz, CDCl3) δ 0.10 (6H, d), 0.93 (9H, s), 1.19 (3H, t), 3.50-3.65 (3H, m), 3.57-3.73 (1H, m), 3.75 (3H, s), 4.37-4.40 (1H, m), 7.18 (2H, d).

1. concentrationThe reaction mixture was concentrated
2. additiondiluted with EtOAc (500 mL)
3. washwashed sequentially with water (4×100 mL) and saturated brine (100 mL)
4. dry with materialThe organic layer was dried (MgSO4)
5. customevaporated
6. customThe residue was purified by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane

ORD record

ord-545e802af563473fa2ebeea550d3f9e0

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08143263B2