tert-Butyl 4-oxopiperidine-1-carboxylate → tert-Butyl 4-(3,3-difluoroazetidin-1-yl)piperidine-1-carboxylate

HRID 2066516ノート

反応式

HRID 2066516 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[F:16][C:17]1([F:21])[CH2:20][NH:19][CH2:18]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.[Cl-].[Na+].O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:19]2[CH2:20][C:17]([F:21])([F:16])[CH2:18]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 5049666Sodium triacetoxyborohydride

生成物 1

HCID 59606191tert-Butyl 4-(3,3-difluoroazetidin-1-yl)piperidine-1-carboxylate収率 88%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 57417360Sodium chloride; water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. stirringstirring
  2. waitwas continued for 17 h
  3. extractionextracted with DCM
  4. customThe organic layer was separated
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by column chromatography

出典と根拠

ORDレコード
ord-c78b4bbc4aa54e96a933ca348f8cc3d5
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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