Chloroacetone → Benzyl N-[(3R)-1-acetonyl-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]carbamate

HRID 2068540ノート

反応式

HRID 2068540 の反応式
[OH-].[K+].[O:3]=[C:4]1[C@H:10]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:9][CH2:8][C:7]2[CH:22]=[CH:23][CH:24]=[CH:25][C:6]=2[NH:5]1.Cl[CH2:27][C:28](=[O:30])[CH3:29].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[CH2:27]([N:5]1[C:6]2[CH:25]=[CH:24][CH:23]=[CH:22][C:7]=2[CH2:8][CH2:9][C@@H:10]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:4]1=[O:3])[C:28]([CH3:29])=[O:30]

参加物

6

反応物 4

HCID 6571Chloroacetone2 回HCID 14797Potassium Hydroxide2 回HCID 2724141Tetrabutylammonium Fluoride2 回HCID 58304068Benzyl N-[(3R)-2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl]carbamate

生成物 1

HCID 58304091Benzyl N-[(3R)-1-acetonyl-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]carbamate収率 69.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

Add powdered potassium hydroxide (KOH) (0.72 g, 12.89 mmol) to a solution of benzyl N-[(3R)-2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl]carbamate (2.0 g, 6.44 mmol), chloroacetone (1.19 g, 12.89 mmol), and tetrabutylammonium fluoride (1.29 mL, 1.29 mmol, 1M solution in THF) in tetrahydrofuran (65 mL). Stir the mixture for approximately 16 hours at ambient temperature. Add additional potassium hydroxide (0.361 g, 6.44 mmol), chloroacetone (0.59 g, 6.44 mmol), tetrabutylammonium fluoride (0.65 mL, 0.65 mmol, 1M solution in THF) and THF (20 mL) to the reaction and stir for approximately 48 hours at ambient temperature. Filter the reaction mixture through diatomaceous earth and concentrate the filtrate under reduced pressure. Purify the residue by flash chromatography (10% ethyl acetate/hexane to 100% ethyl acetate) to give the title compound (1.64 g, 65%): MS (m/z): 389 (M+23).

後処理

  1. customto the reaction
  2. stirringstir for approximately 48 hours at ambient temperature
  3. filtrationFilter the reaction mixture through diatomaceous earth
  4. concentrationconcentrate the filtrate under reduced pressure
  5. customPurify the residue by flash chromatography (10% ethyl acetate/hexane to 100% ethyl acetate)

出典と根拠

ORDレコード
ord-2b6dccf1474a43aeb4047504dd16a12d
出典データセット
uspto-grants-2012_10
特許番号
US08299061B2

反応ノート

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