1-Benzyl-3-methyl-4-piperidone → cis-1-Benzyl-3-methylpiperidin-4-ol

HRID 1821980Notes

Reaction equation

[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH:10]([CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([BH-](C(CC)C)C(CC)C)(CC)C.[Li+]>O1CCCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][C@H:11]([OH:14])[C@H:10]([CH3:15])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Dissolve 1-benzyl-3-methyl-piperidin-4-one (5.0 g, 24.6 mmol) in dry tetrahydrofuran (100 mL) and cool the resulting solution to 0° C. Add 1 mL-lithium tri-sec-butylborohydride (L-Selectride®) solution in tetrahydrofuran (29.6 mL, 29.6 mmol) dropwise over 30 min. After stirring at 0° C. for 1 hr., quench with water (50 mL), extract with ethyl acetate (2×100 mL), wash the combined organic layers with aqueous NaCl solution (100 mL), separate the organic layer, dry over sodium sulfate, filter and concentrate. Purify the residue by silica gel flash chromatography eluting with 5% (2M NH3/methanol)/methylene dichloride to obtain of the title compound as a mixture of enantiomers (3.84 g, 76%). 1H NMR (CDCl3): 7.25 (m, 5H), 3.8 (m, 1H), 3.5 (s, 2H), 2.4 (m, 3H), 2.2 (m, 1H), 1.9 (m, 1H), 1.8 (m, 2H), 0.95 (d, 3H).

Workup

custom, quench with water (50 mL)
extractionextract with ethyl acetate (2×100 mL)
washwash the combined organic layers with aqueous NaCl solution (100 mL)
customseparate the organic layer
dry with materialdry over sodium sulfate
filtrationfilter
concentrationconcentrate
customPurify the residue by silica gel flash chromatography
washeluting with 5% (2M NH3/methanol)/methylene dichloride

Sources & evidence

ORD record: ord-3286a4b7afa94458b9ded6af3a3295c5
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608629B2

Reaction notes

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