Tetrahydrofuran → tert-Butyl 4-(hydroxymethyl)-4-(pyridin-3-yl)piperidine-1-carboxylate

HRID 391457Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)([C:14](O)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O1CCCC1.B.O1CCCC1>CO>[OH:15][CH2:14][C:11]1([C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH2:13][CH2:12]1

Participants

Conditions

Temperature: 0 °C

Procedure

A flask was charged with 1-(tert-butoxycarbonyl)-4-(pyridin-3-yl)piperidine-4-carboxylic acid (4.0 g, 13.1 mmol) and tetrahydrofuran (25 mL). The reaction was placed under nitrogen. To the flask was added borane-tetrahydrofuran complex (1 M in tetrahydrofuran, 26.1 mL, 26.1 mmol) and heated at reflux for 2 h. The reaction was cooled to 0° C. and quenched with methanol (100 mL). The solution was then concentrated in vacuo. The residue was purified via column chromatography (5% methanol/95% dichloromethane) to yield 3.2 g (84%). Mass Spec.: 293.26 (MH)+. LC: tr=1.65 min (Phenomenex-Luna 4.6×50 mm S10, 10% MeOH/90% H2O/0.1% TFA→90% MeOH/10% H2O/0.1% TFA Gradient Time=2 min, Flow rate=4 mL/min).

Workup

temperatureheated
temperatureat reflux for 2 h
customquenched with methanol (100 mL)
concentrationThe solution was then concentrated in vacuo
customThe residue was purified via column chromatography (5% methanol/95% dichloromethane)
customto yield 3.2 g (84%)

Sources & evidence

ORD record: ord-6ecbd9a2c6f240c395de861241088572
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08383821B2

Reaction notes

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