3-Isoxazolecarboxylic acid, 5-[(1R)-1-[[(1,1-diMethylethoxy)carbonyl]aMino]ethyl]-, ethyl ester synthesis

Yield:893444-15-0 75%

Reaction Conditions:

with triethylamine in N,N-dimethyl-formamide at 90; for 1.5 h;

Steps:

1

To compound 1.10 (6.7 g, 39.6 mmol) and 2-chloro-2- hydroxyiminoacetic acid ethyl ester (18.1 g, 120 mmol) in DMF at 9O⁰C (120 mL) was added Et₃N (16.8 mL, 120 mmol) dropwise over 1 hour. The reaction mixture was stirred for 30 minutes, cooled to room temperature, and then concentrated in vacuo. The residue was dissolved in ethyl acetate and H₂O. The aqueous layer was extracted with ethyl acetate (2X); the combined organic layer was extracted with 1N HCl, dried over NaHSO₄, and concentrated in vacuo. Purification by silica gel chromatography (6:1 -> 3:1 hexanes / ethyl acetate) provided compound 1.11 (8.45 g, 75%).

References:

WO2006/65703,2006,A1 Location in patent:Page/Page column 97