Methanamine, N-methoxy-, hydrochloride (1:1) → Nalpha-Boc-Nalpha-methyl-l-valine N-methoxy-N-methylamide

To a cold (0° C.) solution of N-Boc-N-methylvaline (11) (5.0 g, 21.6 mmol), N,O-dimethylhydroxylamine hydrochloride (2.8 g, 28 mmol), and PyBOP® (11.2 g, 22 mmol) in CH2Cl2 (22 mL) was added DIEA (8.4 mL, 75 mmol). After 1 min., the reaction mixture was warmed to room temperature and stirring was continued for 1 h. If the pH value of the mixture was less than 7, the mixture could be treated with a few drops DIEA to allow the reaction to go to completion. The mixture was poured into 200 mL of diethyl ether and the resultant mixture was washed successively with 3 N hydrochloric acid (3×30 mL), saturated aqueous sodium hydrogen carbonate solution (3×30 mL), and saturated aqueous sodium chloride (3×30 mL). The organic layer was dried with magnesium sulfate and the solvent was evaporated, followed by chromatography of the crude product (silica gel, 1:3 diethyl ether-pet. ether), afforded 12 (4.46 g, 75% yield) as a colourless oil. 1H-NMR (200 MHz, CDCl3): 0.84 (d, J=6.6 Hz, 4H, (CH3)2), 0.85 (d, J=6.6 Hz, 2H, (CH3)2), 1.41 (s, 6H, Boc-(CH3)3), 1.44 (s, 3H, Boc-(CH3)3), 2.15-2.30 (m, 1H, CH), 2.75 (s, 1H, NCH3), 2.78 (s, 2H, NCH3), 3.10 (bs, 3H, NCH3), 3.64 (s, 1H, OCH3), 3.68 (s, 2H, OCH3), 4.66 (d, J=10 Hz, 0.4H, CH), 4.95 (d, J=10 Hz, 0.6H, CH); Exact mass calc'd for C13H27N2O4 (M+H)+: 275.19708. Found (DCI): 275.19710. Optical rotation obtained was [α]25 +128.3 (c 2.9, CHCl3).

1. waitwas continued for 1 h
2. customthe reaction
3. washthe resultant mixture was washed successively with 3 N hydrochloric acid (3×30 mL), saturated aqueous sodium hydrogen carbonate solution (3×30 mL), and saturated aqueous sodium chloride (3×30 mL)
4. dry with materialThe organic layer was dried with magnesium sulfate
5. customthe solvent was evaporated

ORD record

ord-a03f9823252647b39a641914ca2ed939

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07579323B1