Methyl chloroformate → 1-tert-Butyl 4-methyl 4-(hydroxymethyl)piperidine-1,4-dicarboxylate

Temperature

0 °C

To a solution of 1-(tert-butoxycarbonyl)-4-(methoxycarbonyl)piperidine-4-carboxylic acid (6 g, 21 mmol) and DIEA (7.3 mL, 42 mmol, 2.0 equiv.) in THF (60 mL) was added methyl chloroformate (1.94 mL, 25 mmol, 1.2 equiv.) at 0° C. The mixture was stirred at 0° C. until the reaction was complete. NaBH4 (3.16 g, 84 mmol, 4.0 equiv.) was added at 0° C. MeOH (10 mL) was then added. The mixture was stirred at 0° C. for 90 min. The reaction mixture was then quenched by saturated NaHCO3 and concentrated to dryness. The residue was dissolved in ethyl acetate, washed with saturated NaHCO3, water and brine, dried over Na2SO4, and concentrated. The resulting residue was purified by column chromatography to give 1-tert-butyl 4-methyl 4-(hydroxymethyl)piperidine-1,4-dicarboxylate (2.6 g, 46%). LRMS (M-Boc+H+) m/z 174.1.

1. stirringThe mixture was stirred at 0° C. for 90 min
2. customThe reaction mixture was then quenched by saturated NaHCO3
3. concentrationconcentrated to dryness
4. dissolutionThe residue was dissolved in ethyl acetate
5. washwashed with saturated NaHCO3, water and brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. customThe resulting residue was purified by column chromatography

ORD record

ord-c02f69a24512453783efbfc8e04f8067

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071625B2