Trifluoroacetic acid → 4-(3,3-Difluoroazetidin-1-yl)piperidine

HRID 2066517ノート

反応式

HRID 2066517 の反応式
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:17][C:16]([F:19])([F:18])[CH2:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:19][C:16]1([F:18])[CH2:17][N:14]([CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)[CH2:15]1

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 59606191tert-Butyl 4-(3,3-difluoroazetidin-1-yl)piperidine-1-carboxylate

生成物 1

HCID 596056804-(3,3-Difluoroazetidin-1-yl)piperidine収率 77%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (1.0 g, 5.0 mmol) in DCE (50 mL) was added 3,3-difluoroazetidine hydrochloride (712 mg, 5.5 mmol). The mixture was stirred at RT for 15 min, then sodium triacetoxyborohydride (1.59 g, 7.5 mmol) was added and stirring was continued for 17 h. The reaction mixture was diluted with brine and extracted with DCM. The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by column chromatography to give 4-(3,3-difluoroazetidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester as a pale yellow solid (1.2 g, 88%). To a solution of 4-(3,3-difluoro-azetidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (552 mg, 2.0 mmol) in DCM (4 mL) was added TFA (2 mL) and the resulting mixture was stirred at RT for 45 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH then eluted with 2 M NH3 in MeOH to give the title compound as a pale yellow solid (271 mg, 77%).

後処理

  1. washThe cartridge was washed with MeOH
  2. washthen eluted with 2 M NH3 in MeOH

出典と根拠

ORDレコード
ord-a433c89a31954b1090d921f67320a7d7
出典データセット
uspto-grants-2012_10
特許番号
US08293735B2

反応ノート

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