Aluminium lithium hydride → 3-Benzylamino-4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester

HRID 2174964Notes

Reaction equation

[H-].[H-].[H-].[H-].[Li+].[Al+3].C([O:9][C:10]([CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH:13]1[NH:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=O)C>C1COCC1>[C:21]([O:20][C:18]([N:15]1[CH2:16][CH2:17][CH:12]([CH2:10][OH:9])[CH:13]([NH:25][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:14]1)=[O:19])([CH3:24])([CH3:22])[CH3:23]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of LiAlH4 (2M in THF, 14 mmol in 25 ml THF), cooled to 0° C., was slowly added a solution of 3-benzylamino-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (4.53 g, 12.5 mmol) in THF (25 mL). The reaction mixture was stirred at 0° C. for 15 min and then at room temperature for 2 h. The reaction mixture was again cooled to 0° C. and quenched with Na2SO4, 10 H2O and stirred for 16 h. The reaction mixture was filtered, washed with THF and concentrated to yield title compound (3.69 g, 92%). MS (ESI) mass calcd. for C18H28N2O3, 320.43; m/z found, 321.3 [M+H]+. 1H NMR (CDCl3): 7.42-7.19 (m, 5H), 5.64-4.97 (m, 1H), 4.57-4.0 (m, 1H), 3.99-3.82 (m, 2H), 3.79-3.56 (m, 3H), 3.04-2.58 (m, 3H), 1.95-1.79 (m, 2H), 1.74-1.55 (m, 2H), 1.47 (s, 9H).

Workup

waitat room temperature for 2 h
temperatureThe reaction mixture was again cooled to 0° C.
customquenched with Na2SO4, 10 H2O
stirringstirred for 16 h
filtrationThe reaction mixture was filtered
washwashed with THF
concentrationconcentrated

Sources & evidence

ORD record: ord-84bd2efa5cb245a5a7f2c701f32f9b04
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09062044B2

Reaction notes

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