Hydrochloric Acid → 3-[(4-Fluoro-benzyl)-methyl-carbamoyl]-2-hydroxy-acrylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

N-(4-Fluoro-benzyl)-N-methyl-acetamide (3.6 grams, 20 mmol) was dissolved in 20 mL of THF and cooled to −78° C. To this was added 40 mL of 1M LiHMDS (in THF) and the resulting solution stirred for 30 min. Next dimethyl oxalate (3.5 grams, 30 mmol) dissolved in 8 mL of THF is added and the reaction stirred for 2 h at −78° C., then warmed to 0° C. and stirred an additional 30 min. To this was added 1N HCl and the mixture then extracted with EtOAc. The organic layer was washed with saturated NaCl, dried over Na2SO4, filtered and the solvent removed. The crude product was purified by column chromatography (4×4 cm SiO2, 80:20 Hex/EtOAc) to yield 4.3 grams solid (80% yield). HRMS (M+H) calcd for C13H15NO4F: 268.0985; found: 268.0983. Anal calcd for C13H14NO4F: C, 58.42; H, 5.28; N, 5.24. found: C, 58.48; H, 5.21; N, 5.26. 1H NMR and 13C NMR show a mixture of rotamers at room temperature. 1H NMR (500 MHz, CDCl3) δ: 3.00 (s), 3.86 (s), 3.89 (s), 4.55 (s), 6.29 (s), 6.31 (s), 7.00–7.24 (overlapping m, 4). 13C NMR δ; 33.43, 34.79, 49.97, 52.63, 52.97, 93.27, 93.55, 115.63, 115.80, 115.95, 116.13, 128.36, 128.42, 129.71, 129.78, 131.32, 132.03, 159.70, 161.40, 163.25, 163.35, 170.93, 171.16.

Provenance & Evidence