3-Bromothiophene → 1-Piperidinecarboxylic acid, 3-(hydroxy-3-thienylmethyl)-, 1,1-dimethylethyl ester

HRID 2274158Notes

Reaction equation

Br[C:2]1[CH:6]=[CH:5][S:4][CH:3]=1.C([Mg]Cl)(C)C.[Cl-].[Li+].[CH:14]([CH:16]1[CH2:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]1)=[O:15]>O1CCCC1>[OH:15][CH:14]([C:2]1[CH:6]=[CH:5][S:4][CH:3]=1)[CH:16]1[CH2:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]1

Participants

Conditions

Temperature: 5 °C

Procedure

Under a nitrogen atmosphere, 5.0 g (30.67 mmol) of 3-bromothiophene in 5 ml of tetrahydrofuran were slowly added dropwise to 24.77 ml (32.2 mmol) of isopropylmagnesium chloride/lithium chloride complex (1.3 M in tetrahydrofuran) at 5° C. After the mixture had been stirred at 5° C. for 0.5 h, 6.54 g (30.67 mmol) of tert-butyl 3-formylpiperidine-1-carboxylate were slowly added dropwise. After removal of the cold bath, the reaction mixture was stirred for a further 1 h. Conventional work-up gave 10.3 g of tert-butyl 3-(hydroxythiophen-3-ylmethyl)piperidine-1-carboxylate; HPLC/MS (M+H-tBuO)+=244 as oil (diastereomers).

Workup

customAfter removal of the cold bath
stirringthe reaction mixture was stirred for a further 1 h

Sources & evidence

ORD record: ord-ed61637d30d34ee388319355daafd869
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09126952B2

Reaction notes

Loading…