Potassium Bromide → 3-{(S)-4-[(E)-3-(3-Chloro-4-fluoro-phenyl)-acryloyl]-3-methyl-2-oxo-piperazin-1-yl}-propionic acid

HRID 2095582ノート

反応式

HRID 2095582 の反応式
[C:1](=[O:4])([O-])[OH:2].[Na+].[Cl:6][C:7]1[CH:8]=[C:9](/[CH:14]=[CH:15]/[C:16]([N:18]2[CH2:23][CH2:22][N:21]([CH2:24][CH2:25]CO)[C:20](=[O:28])[C@@H:19]2[CH3:29])=[O:17])[CH:10]=[CH:11][C:12]=1[F:13].[Br-].[K+].Cl[O-].[Na+]>ClCCl>[Cl:6][C:7]1[CH:8]=[C:9](/[CH:14]=[CH:15]/[C:16]([N:18]2[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][C:1]([OH:2])=[O:4])[C:20](=[O:28])[C@@H:19]2[CH3:29])=[O:17])[CH:10]=[CH:11][C:12]=1[F:13]

参加物

6

反応物 4

HCID 253877Potassium BromideHCID 516892Sodium BicarbonateHCID 23665760Sodium HypochloriteHCID 44541810(S)-4-[(E)-3-(3-Chloro-4-fluoro-phenyl)-acryloyl]-1-(3-hydroxy-propyl)-3-methyl-piperazin-2-one

生成物 1

HCID 670743863-{(S)-4-[(E)-3-(3-Chloro-4-fluoro-phenyl)-acryloyl]-3-methyl-2-oxo-piperazin-1-yl}-propionic acid収率 4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Saturated aqueous sodium hydrogencarbonate solution (15 ml) was added to a solution of (S)-4-[(E)-3-(3-chloro-4-fluoro-phenyl)-acryloyl]-1-(3-hydroxy-propyl)-3-methyl-piperazin-2-one (PCT Int. Appl. WO 2009010429 A2; 5.70 g, 16.1 mmol), potassium bromide (191 mg, 1.61 mmol), and 2,2,6,6-tetramethylpiperidin-1-oxyl (25 mg, 0.16 mmol) in dichloromethane (300 mL). Sodium hypochlorite solution (10% in water, 9.6 ml, 16 mmol) was added portionwise at 0° C., and the course of the oxidation was monitored by thin layer chromatography. After all starting material had reacted, the reaction mixture was washed with sodium hydrogencarbonate, and the aqueous layer was extracted twice with dichloromethane. The organic phases were pooled, dried over magnesium sulfate, filtered, and evaporated, thus affording 3-{(S)-4-[(E)-3-(3-chloro-4-fluoro-phenyl)-acryloyl]-3-methyl-2-oxo-piperazin-1-yl}-propionaldehyde (5.15 g, 91%). The aqueous layer was acidified to pH 3 with 1 M aq. hydrochloric acid solution and extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and evaporated to afford the title compound (254 mg, 4%). Colorless gum, MS: 367.3 (M−H, Cl)−.

後処理

  1. customAfter all starting material had reacted
  2. washthe reaction mixture was washed with sodium hydrogencarbonate
  3. extractionthe aqueous layer was extracted twice with dichloromethane
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. extractionextracted with dichloromethane
  8. dry with materialThe organic layer was dried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated

出典と根拠

ORDレコード
ord-1f721d8e0f6e44c5a6be5f315e0bd234
出典データセット
uspto-grants-2013_05
特許番号
US08445674B2

反応ノート

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