Methyl iodide → (R)-2-((tert-butoxycarbonyl)amino)-3-methoxy-3-methylbutanoic acid

Participants

Reaction Steps

To a solution of sodium hydride suspension in mineral oil (60% wt) (3.86 g, 96 mmol) in dry THF (60 mL) were added (R)-2-((tert-butoxycarbonyl)amino)-3-hydroxy-3-methylbutanoic acid (7.5 g, 32.2 mmol) in THF (50 mL) at 0° C. slowly. After stirring for 1 h at room temperature, iodomethane (4.31 ml, 38.6 mmol) was added. The reaction mixture was stirred at room temperature overnight. After quenched with water, the reaction mixture was extracted by ether. The aqueous layers was acidify to pH=3 by adding 6 N HCl, then extracted by EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered though Buchner funnel, and concentrated to yield crude (R)-2-((tert-butoxycarbonyl)amino)-3-methoxy-3-methylbutanoic acid (7 g, 28.3 mmol, 88%), which was used in next step reaction without purification. LC/MS (uplc): MH+ 160.1, 0.68 min.

Provenance & Evidence