Borane;tetrahydrofuran → tert-Butyl 4-(hydroxymethyl)-4-(pyridin-3-yl)piperidine-1-carboxylate

HRID 656515Notes

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].B.C1COCC1>O1CCCC1>[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, 13.06 mmol) and tetrahydrofuran (25 mL). The reaction was placed under N2. To the flask was added Borane/THF (26.1 mL of 1M soln, 26.1 mmol) and set to reflux for 2 hours. The reaction was cooled to 0° C. and quenched with MeOH (100 mL). The solution was then conc. in vacuo. The residue was purified via column chromatography (5% MeOH/95% CH2Cl2) to yield 3.2 g (84%). Mass Spec.: 293.26 (MH)+. LC: tr=1.65 min HPLC Method 1. 1H-NMR (CD3OD, 400 MHz) δ 8.56 (s, 1H), 8.45 (d, 1H), 8.10 (d, 1H), 7.59 (m, 1H), 3.67 (m, 2H), 3.56 (s, 2H), 3.11 (t, 2H), 2.11 (d, 2H), 1.85 (m, 2H), 1.43 (s, 9H).

Workup

temperatureto reflux for 2 hours
customquenched with MeOH (100 mL)
customThe residue was purified via column chromatography (5% MeOH/95% CH2Cl2)
customto yield 3.2 g (84%)
customtr=1.65 min HPLC Method 1

Sources & evidence

ORD record: ord-d8c1208fa68d4a48a6535a3bed89e41e
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08071778B2

Reaction notes

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