4-Methylmorpholine → Tert-butyl 4-((2-oxo-2-(3-(trifluoromethyl)phenyl)ethyl)carbamoyl)piperidine-1-carboxylate

HRID 419698ノート

反応式

HRID 419698 の反応式
CN1CCOCC1.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([C:21]([OH:23])=O)[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].ClC(OCC(C)C)=O.Cl.[NH2:33][CH2:34][C:35]([C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[CH:38]=1)=[O:36]>C1COCC1>[O:36]=[C:35]([C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:44])([F:45])[F:46])[CH:38]=1)[CH2:34][NH:33][C:21]([CH:18]1[CH2:17][CH2:16][N:15]([C:13]([O:12][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:14])[CH2:20][CH2:19]1)=[O:23]

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 133658852-Amino-1-(3-(trifluoromethyl)phenyl)ethan-1-one hydrochloride

生成物 1

HCID 57751897Tert-butyl 4-((2-oxo-2-(3-(trifluoromethyl)phenyl)ethyl)carbamoyl)piperidine-1-carboxylate収率 60.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Add N-methylmorpholine (13.0 mL, 118 mmol) to a solution of 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (11.2 g, 48.8 mmol) in THF (400 mL) at −10° C. and stir for 5 min. Add isobutyl chloroformate (5.1 mL, 38.8 mmol) and continue stirring at −10° C. for 2 h. Add 2-amino-1-(3-(trifluoromethyl)phenyl)ethanone hydrochloride (9.35 g, 39.0 mmol) and continue stirring for 1 h. Add methylene chloride (500 mL) to the mixture and filter. Wash the filtrate with sat. aqueous sodium bicarbonate (400 mL) and concentrate in vacuo. Purify the residue by silica gel chromatography (330 g RediSep column, eluting with a gradient of 0% to 100% ethyl acetate:hexane, 6.0 L) to provide tert-butyl 4-(2-oxo-2-(3-(trifluoromethyl)phenyl)ethylcarbamoyl)piperidine-1-carboxylate (9.72 g, 60%).

後処理

  1. filtrationAdd methylene chloride (500 mL) to the mixture and filter
  2. washWash the filtrate with sat. aqueous sodium bicarbonate (400 mL)
  3. concentrationconcentrate in vacuo
  4. customPurify the residue by silica gel chromatography (330 g RediSep column
  5. washeluting with a gradient of 0% to 100% ethyl acetate

出典と根拠

ORDレコード
ord-cba451bc92a44d7baed86f5a90e726b8
出典データセット
uspto-grants-2012_01
特許番号
US08093383B2

反応ノート

読み込み中…