Borane;tetrahydrofuran → Tert-butyl 4-(2-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[F:23])([C:14](O)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B.O1CCCC1>O1CCCC1>[F:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[C:11]1([CH2:14][OH:15])[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]1Participants
Procedure
A flask was charged with 1-(tert-butoxycarbonyl)-4-(2-fluorophenyl)piperidine-4-carboxylic acid (1.51 g, 4.6 mmol) and tetrahydrofuran (10 mL). The reaction was placed under nitrogen. To the flask was added borane-tetrahydrofuran complex (1 M in tetrahydrofuran, 9.2 mL, 9.2 mmol). The reaction was allowed to stir at rt for 48 hr. The reaction was cooled to 0° C. and quenched with methanol (50 mL). The solution was then concentrated in vacuo. The residue was purified via column chromatography (25% ethyl acetate/75% hexanes→60% ethyl acetate/hexanes) to yield 1.0 g (70%) of the desired alcohol. 1H-NMR (CDCl3, 400 MHz) δ ppm 7.26 (m, 2H), 7.11 (m, 1H), 7.01 (m, 1H), 3.72 (m, 4H), 3.09 (m, 2H), 2.27 (m, 2H), 1.79 (m, 2H), 1.42 (s, 9H). Mass Spec.: 332.18 (MNa)+. LC: tr=3.301 min (Phenomenex-Luna 4.6×50 mm S10, 10% MeOH/90% H2O/0.1% TFA→90% MeOH/10% H2O/0.1% TFA Gradient Time=4 min, Flow rate=4 mL/min).
Workup
- temperatureThe reaction was cooled to 0° C.
- customquenched with methanol (50 mL)
- concentrationThe solution was then concentrated in vacuo
- customThe residue was purified via column chromatography (25% ethyl acetate/75% hexanes→60% ethyl acetate/hexanes)
Sources & evidence
- ORD record
- ord-809c3b8698a444fe8780c2d5a2455149
- Source dataset
- uspto-grants-2013_02
- Patent number
- US08383821B2
Reaction notes
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