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

HRID 1976077Notes

Reaction equation

B.O1CCCC1.[C:7]([O:11][C:12]([N:14]1[CH2:22][CH2:21][CH:17]([C:18](O)=[O:19])[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].O.C([O-])([O-])=O.[K+].[K+]>O1CCCC1>[C:7]([O:11][C:12]([N:14]1[CH2:22][CH2:21][CH:17]([CH2:18][OH:19])[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]

Participants

Conditions

Temperature: 0 °C

Procedure

Borane-tetrahydrofuran (1 M, 25 mL, 25 mmol) was added slowly to N-tert-butoxycarbonylisonipecotic acid (5.73 g, 25 mmol), as prepared in the preceding step, in tetrahydrofuran (50 mL) at 0° C. (ice-bath) over 30 min. The 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 mixture was extracted with ethyl acetate (3×50 mL). The organic phase was washed sequentially with saturated NaHCO3 (2×50 mL) and brine (2×50 mL), and dried over Na2SO4. The solvent was removed in vacuo, and the residue was 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, 2 H), 1.42 (s, 9 H), 1.67 (m, 4 H), 2.67 (t, 2 H, J=12.5 Hz), 3.46 (d, 2 H, J=3.0 Hz), and 4.09 (d, 2 H, J=3.6 Hz).

Workup

temperaturewarmed up to room temperature for 6 h
extractionThe mixture was extracted with ethyl acetate (3×50 mL)
washThe organic phase was washed sequentially with saturated NaHCO3 (2×50 mL) and brine (2×50 mL)
dry with materialdried over Na2SO4
customThe solvent was removed in vacuo
customthe residue was purified by flash column chromatography (1:1 hexane/ethyl acetate)

Sources & evidence

ORD record: ord-9013d2548e824e658f6a89823e259a54
Source dataset: uspto-grants-2001_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06225302B1

Reaction notes

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