4-Methylmorpholine → tert-butyl N-(1-hydroxy-2,4-dimethylpentan-2-yl)carbamate

To a stirred solution of 2-((tert-butoxycarbonyl)amino)-2,4-dimethylpentanoic acid (1.6 g, 6.52 mmol) in tetrahydrofuran (40 mL) cooled to −10° C. under nitrogen atmosphere was added N-methylmorpholine (0.860 mL, 7.83 mmol) followed by isobutyl chloroformate (1.028 mL, 7.83 mmol) dropwise and the reaction mixture was stirred for 30 min. The reaction mixture was then filtered and the filtrate was added dropwise to a suspension of NaBH4 (0.494 g, 13.04 mmol) in water (20.0 mL). The reaction mixture was stirred for 10 min then diluted with ethyl acetate (30 mL). The organic layer was separated and washed with brine (2×20 mL), dried over (Na2SO4) and evaporated under reduced pressure. The residue was purified by silica gel chromatography (30% ethyl acetate and pet ether) to afford tert-butyl(1-hydroxy-2,4-dimethylpentan-2-yl)carbamate (1.1 g, 4.76 mmol, 73% yield) as an oil. 1H NMR (400 MHz, DMSO-d6) δ 6.09 (s, 1 H), 4.61 (t, J=7.6 Hz, 1 H), 3.35 (m, 2 H), 1.8-1.6 (m, 2 H), 1.44-1.35 (m, 10 H), 1.09 (s, 3 H), 0.86 (m, 6 H).

1. filtrationThe reaction mixture was then filtered
2. stirringThe reaction mixture was stirred for 10 min
3. customThe organic layer was separated
4. washwashed with brine (2×20 mL)
5. dry with materialdried over (Na2SO4)
6. customevaporated under reduced pressure
7. customThe residue was purified by silica gel chromatography (30% ethyl acetate and pet ether)

ORD record

ord-3257e40ff90241319353d0351390f827

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08703953B2