Hexane → 3-{4-[4-(Tert-butoxycarbonylaminocarboxymethyl)-phenoxy]-phenyl}-acrylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Sodium hydride (60% in mineral oil, 4.03 g, 100.0 mmol) was washed with anhydrous hexane (3×50 mL) under an atmosphere of argon. Dry THF (200 mL) was added and cooled to 0-5° C. A solution of trimethylphosphonoacetate (8.2 mL, 50.0 mmol) in dry THF (35 mL) was added dropwise to the above mixture with stirring. After about 5 min, a solution of the aldehyde 29 (17.0 g, 46.0 mmol) in dry THF (35 mL) was added and the reaction mixture was then brought up to room temperature and stirred. After 30 min, the clear reaction mixture was quenched with 10% citric acid (50 mL) and further acidified to pH ˜2.0 with 2.0 M HCl. THF was evaporated under reduced pressure and the resulting oily material was extracted with EtOAc (2×400 mL). The organic layer was extracted with water (3×500 mL), and brine (1×500 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield the unsaturated ester 30 (20.0 g, quantitative yield) as a crude product that was taken for the next step without further purification. 1H NMR (400 MHz, DMSO-d6): 12.9 (br, 1H), 7.75 (d, J=8.8 Hz, 2H), 7.65 (d, J=12.0 Hz, 1H), 7.60 (d, J=8.4 Hz, 1H), 7.05 (d, J=8.8 Hz, 2H), 7.01 (d, J=8.8 Hz, 2H), 6.56 (d, J=12.0 Hz, 1H), 5.12 (d, J=8.0 Hz, 1H), 3.72 (s, 3H), 1.40 (s, 9H).

Provenance & Evidence