Carbamic acid, N-[2-(methoxymethylamino)-1-methyl-2-oxoethyl]-, 1,1-dimethylethyl ester synthesis

Yield:342603-65-0 41%

Reaction Conditions:

Stage #1: L-N-Boc-Alawith benzotriazol-1-ol;1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride;triethylamine in N,N-dimethyl-formamide at 20; for 0.5 h;
Stage #2: N,O-dimethylhydroxylamine*hydrochloride in N,N-dimethyl-formamide at 0 - 20; for 12 h;

Steps:

127 tert-butyl (1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate (ID )

To a stirred solution of (tert-butoxycarbonyl)alanine (IC, 10.0 g, 52.8 mmol) in DMF (100 mL) was added EDCI.HC1 (15.1 g, 79.2 mmol) and HOBT (10.8 g, 79.2 mmol) followed by triethylamine (15 mL, 105.7 mmol) and the reaction mixture was stirred at RT for 30 min. To the resulting reaction mixture, N,0-dimethylhydroxylamine hydrochloride (15.4 g, 158.5 mmol) was added at 0C and the reaction mixture was stirred at RT for 12 h. The progress of reaction was monitored by TLC. After completion of the reaction, the reaction mixture was quenched with ice cold water and the product was extracted with EtOAc. The combined organic layer was dried over anhydrous Na2S04 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using 30% EtOAc/hexane to afford compound ID (5.0 g, 41.0%) as an off white solid. 1H NMR (400 MHz, DMSO-d6): _ 7.04 (d, 7 = 7.6 Hz, 1H), 4.41-4.37 (m, 1H), 3.72 (s, 3H), 3.09 (s, 3H), 1.36 (s, 9H), 1.14 (d, J = 7.2 Hz, 3H).

References:

WO2018/165520,2018,A1 Location in patent:Page/Page column 233-234