Water → Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Temperature

0 °C

N-(tert-butoxycarbonyl)-isonipecotic acid (5.73 g, 25 mmol), as prepared in the preceding step, was dissolved in tetrahydrofuran (50 mL) and cooled to 0° C. (ice-bath). Borane-tetrahydrofuran complex (1M, 25 mL, 25 mmol) was added slowly over 30 min. The reaction mixture was stirred at 0° C. overnight and then warmed up to room temperature for 6 h. Water (10 mL) was added slowly and then K2CO3 (5 g in 50 mL water) was added. The reaction mixture was extracted into ethyl acetate (3×50 mL). The organic phase was washed with saturated NaHCO3 (2×50 mL), brine (2×50 mL), dried over Na2SO4, and concentrated in vacuo. The residue was then purified by flash column chromatography (1:1 hexane:ethyl acetate) to give the title compound as white crystals (4.55 g, 84%). 1H-NMR (300 MHz, CDCl3) δ 1.13 (m, 2H), 1.42 (s, 9H), 1.67 (m, 4H), 2.67 (t, 2H), 3.46 (d, 2H), 4.09 (d, 2H).

1. additionBorane-tetrahydrofuran complex (1M, 25 mL, 25 mmol) was added slowly over 30 min
2. temperaturewarmed up to room temperature for 6 h
3. extractionThe reaction mixture was extracted into ethyl acetate (3×50 mL)
4. washThe organic phase was washed with saturated NaHCO3 (2×50 mL), brine (2×50 mL)
5. dry with materialdried over Na2SO4
6. concentrationconcentrated in vacuo
7. customThe residue was then purified by flash column chromatography (1:1 hexane:ethyl acetate)

ORD record

ord-ee7fdfc41035405e9b73c2acd44153ac

Source dataset

uspto-grants-1998_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05792769