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

HRID 2095582Notes

Reaction equation

HRID 2095582 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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)−.

Workup

  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

Sources & evidence

ORD record
ord-1f721d8e0f6e44c5a6be5f315e0bd234
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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