Sodium borohydride → rac-tert-butyl (3R,4R)-3-fluoro-4-hydroxypiperidine-1-carboxylate

HRID 1505675Notes

Reaction equation

[BH4-].[Na+].[F:3][CH:4]1[C:9](=[O:10])[CH2:8][CH2:7][N:6]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:5]1>CO>[C:14]([O:13][C:11]([N:6]1[CH2:7][CH2:8][C@@H:9]([OH:10])[C@H:4]([F:3])[CH2:5]1)=[O:12])([CH3:17])([CH3:15])[CH3:16]

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium borohydride (1.53 g, 40.5 mmol) was added to a stirred solution of tert-butyl 3-fluoro-4-oxopiperidine-1-carboxylate (OmegaChem, 8 g, 36.8 mmol) in dry methanol (100 mL) maintained at 0° C. The reaction mixture was stirred at same temperature for 45 min, it was then quenched with dry acetone (20 mL) and evaporated under reduced pressure. The residue was diluted with EtOAc and washed with water and brine. It was dried over sodium sulfate, filtered and concentrated. Purification by flash chromatography on silica (Pet. Ether: EtOAc, 80:20) afforded the titled compound as white solid (4.0 g, 50%). 1H NMR (400 MHz, DMSO-d6) δ 4.61 (ddd, J=39, 8.6, 3.2 Hz, 1H), 3.93 (m, 2H), 3.71 (bs, 1H), 3.42 (brs, 1H), 3.06-3.00 (m, 1H), 1.88-1.83 (m, 2H), 1.45 (s, 9H). HPLC (Condition A): Rt 2.7 min (purity 97%).

Workup

customit was then quenched with dry acetone (20 mL)
customevaporated under reduced pressure
additionThe residue was diluted with EtOAc
washwashed with water and brine
dry with materialIt was dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customPurification by flash chromatography on silica (Pet. Ether: EtOAc, 80:20)

Sources & evidence

ORD record: ord-e0124b02996647f58a453c91d19d042c
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216991B2

Reaction notes

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