2-Bromothiophene → HCID 58179496, compound

HRID 1518552Notes

Reaction equation

Br[C:2]1[S:3][CH:4]=[CH:5][CH:6]=1.[O:7]=[C:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1>C1COCC1>[OH:7][C:8]1([C:2]2[S:3][CH:4]=[CH:5][CH:6]=2)[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:12][CH2:13]1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 2-bromothiophene in THF (25 ml) was added drop wise to a suspension of Mg turnings in THF (100 mL). The mixture was stirred for 30 minutes, cooled to 0° C., and a solution of tert-butyl 4-oxopiperidine-1-carboxylate (25.0 g, 125.4 mmol) in THF (25 mL) was added dropwise. The reaction mixture was slowly warmed to RT and stirred for 1 hour until complete consumption of 2-bromothiophene was indicated by TLC. The reaction was quenched with sat. aq. NH4Cl solution (50 mL), extracted with EtOAc (200 mL), washed with H2O (50 mL) and brine solution, dried (Na2SO4), filtered, and evaporated to afford crude product as light brown oil. Purification by silica gel chromatography (25% EtOAc/hexanes) yielded tert-butyl 4-hydroxy-4-(thiophen-2-yl)piperidine-1-carboxylate (14.0 g, 40% yield).

Workup

temperatureThe reaction mixture was slowly warmed to RT
customThe reaction was quenched with sat. aq. NH4Cl solution (50 mL)
extractionextracted with EtOAc (200 mL)
washwashed with H2O (50 mL) and brine solution
dry with materialdried (Na2SO4)
filtrationfiltered
customevaporated
customto afford crude product as light brown oil
customPurification by silica gel chromatography (25% EtOAc/hexanes)

Sources & evidence

ORD record: ord-fee8caa0649246c0be15d8983f3a365e
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08232406B2

Reaction notes

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