Methyl bromoacetate → Methyl 2-(5-methyl-2,4-dioxothiazolidin-5-yl)acetate

Temperature

-40 °C

To a stirred solution of Compound 1d (300 mg, 2.3 mmol) in THF (20 mL) at −40° C. was added 2 M LDA in heptane/THF/benzene (2.4 mL, 4.8 mmol) dropwise. After 15 minutes, methyl 2-bromoacetate (0.30 mL, 3.2 mmol) was added and the reaction mixture stirred at −40° C. for 2 h then quenched by dropwise addition of AcOH (0.8 mL). The reaction mixture was diluted with EtOAc, and the organic portion washed with water (2×), brine (2×), dried (Na2SO4), filtered and concentrated under reduced pressure. The product was purified by silica gel chromatography eluting with 0-100% EtOAc/hexanes to afford Compound 1e (180 mg, 39%) as a clear oil. LCMS=1.06 min using analytical method (B), 225.9 (M+Na). 1H NMR (400 MHz, CDCl3) δ 3.75 (s, 3H), 3.24-2.84 (m, 2H), 1.81 (s, 3H).

1. customthen quenched by dropwise addition of AcOH (0.8 mL)
2. additionThe reaction mixture was diluted with EtOAc
3. washthe organic portion washed with water (2×), brine (2×)
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe product was purified by silica gel chromatography
8. washeluting with 0-100% EtOAc/hexanes

ORD record

ord-64e413c246cd497db658313f536e6751

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08680090B2