Methanol → 4-(2-Hydroxymethylthiophen-3-yl)piperidine-1-carboxylic Acid t-Butyl Ester
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:18]=[CH:17][S:16][C:15]=2[C:19](OC)=[O:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:18]=[CH:17][S:16][C:15]=2[CH2:19][OH:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]Participants
Procedure
A solution of 4-(2-methoxycarbonylthiophen-3-yl)piperidine-1-carboxylic acid t-butyl ester (2.4 g, 7.4 mmol, 1.0 eq.) in THF (20 mL) was degassed and purged with nitrogen (2×). Borane dimethyl sulfide complex (35 mL, 70 mmol, 110.8 eq.) was added at room temperature and the mixture was heated to reflux overnight. The mixture was allowed to cool to room temperature and MeOH (20 mL) was slowly added. The mixture was then concentrated under vacuum. The addition of MeOH (20 mL) and concentrating was repeated two additional times. The product was applied onto a silica gel column and purified by chromatography with PE/EtOAc (10:1). The product was then purified by preparative HPLC to yield the title compound (1.5 g) as a yellow oil, which gradually solidified.
Workup
- custompurged with nitrogen (2×)
- additionBorane dimethyl sulfide complex (35 mL, 70 mmol, 110.8 eq.) was added at room temperature
- temperaturethe mixture was heated
- temperatureto reflux overnight
- concentrationThe mixture was then concentrated under vacuum
- additionThe addition of MeOH (20 mL)
- concentrationconcentrating
- custompurified by chromatography with PE/EtOAc (10:1)
- customThe product was then purified by preparative HPLC
Sources & evidence
- ORD record
- ord-1b60599f6b544da28fbe9b2fc13f70a5
- Source dataset
- uspto-grants-2013_09
- Patent number
- US08530663B2
Reaction notes
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