Ethyl 3-(4-benzylpiperidin-1-yl)butyrate → 4-Benzyl-1-(3-hydroxy-1-methylpropyl)piperidine

HRID 1861776

Reaction equation

[CH2:1]([CH:8]1[CH2:13][CH2:12][N:11]([CH:14]([CH3:21])[CH2:15][C:16](OCC)=[O:17])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH2:1]([CH:8]1[CH2:9][CH2:10][N:11]([CH:14]([CH3:21])[CH2:15][CH2:16][OH:17])[CH2:12][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of ethyl 3-(4-benzylpiperidin-1-yl)butyrate (0.60 g, 2.0 mmol) in dry THF (10 mL) was added portionwise LiAlH4 (0.15 g, 3.9 mmol). The resulting heterogeneous mixture was stirred at 25° C. for 2 h then quenched with MeOH. The resulting mixture was diluted with EtOAc (100 mL), washed with NH4Cl (100 mL) and brine (100 mL), dried and was concentrated under reduced pressure. The crude compound was purified by filtration on silica gel using CH2Cl2/MeOH as solvent to afford the title compound as a colorless solid (0.38 g, 80%): mp 74-76° C.; 1H NMR (CDCl3) δ1.00 (d, J=6.6 Hz, 3H), 1.15-1.45 (m, 3H), 1.50-1.65 (m, 1H), 1.65-1.80 (m, 2H), 1.85-2.15 (m, 3H), 2.40-2.60 (m, 3H), 2.82 (bd, J=11.1 Hz, 1H), 2.90-3.10 (m, 2H), 3.80-4.00 (m, 2H), 6.55 (bs, 1H), 7.19 (t, J=7.2 Hz, 2H), 7.24 (d, J=6.9 Hz, 1H), 7.32 (t, J=7.2 Hz, 2H); MS (m/z) 247, 248, 232, 202, 91. Anal. Calcd for C16H25NO: C, 77.68, H 10.18; N, 5.66. Found C, 77.56; H 10.22; N, 5.63.

Workup

customthen quenched with MeOH
additionThe resulting mixture was diluted with EtOAc (100 mL)
washwashed with NH4Cl (100 mL) and brine (100 mL)
customdried
concentrationwas concentrated under reduced pressure
filtrationThe crude compound was purified by filtration on silica gel

Sources & evidence

ORD record: ord-d041f354dfe94a9dacf2055371649c04
Source dataset: uspto-grants-2003_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06534522B2

Linked notes

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