Potassium Bromide → HCID 67951276, compound

HRID 2401382Notes

Reaction equation

HRID 2401382 reaction equation
[NH2:1][C@H:2]([C:11]1[O:15][N:14]=[C:13]([CH3:16])[C:12]=1[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([F:23])[C:18]=1[CH2:24][OH:25])[CH2:3][C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].CC1(C)N([O])C(C)(C)CCC1.[Br-].[K+].Cl[O-].[Na+]>C(Cl)Cl>[F:23][C:19]1[C:18]2[C:24](=[O:25])[NH:1][C@@H:2]([CH2:3][C:4]([O:6][C:7]([CH3:10])([CH3:8])[CH3:9])=[O:5])[C:11]3[O:15][N:14]=[C:13]([CH3:16])[C:12]=3[C:17]=2[CH:22]=[CH:21][N:20]=1

Participants

6

Reactant 4

HCID 253877Potassium BromideHCID 2724126TempoHCID 23665760Sodium HypochloriteHCID 67951269HCID 67951269, compound

Product 1

HCID 67951276HCID 67951276, compoundYield 22.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (3S)-tert-butyl 3-amino-3-(4-(2-fluoro-3-(hydroxymethyl)pyridin-4-yl)-3-methylisoxazol-5-yl)propanoate (200 mg, 0.569 mmol) and TEMPO (4.45 mg, 0.028 mmol) in CH2Cl2 (5 mL) at 0° C. was sequentially added potassium bromide (33.9 mg, 0.285 mmol) and an aqueous solution of sodium hypochlorite (˜0.35M buffered to pH ˜8.6 with sodium bicarbonate) (4.879 mL, 1.708 mmol). The reaction was vigorously stirred (to produce an emulsion) at 0° C. for 45 min before diluting with CH2Cl2. The product was extracted with CH2Cl2 (repeated once), with CH2Cl2/MeOH (95:5) (repeated once) and CH2Cl2/TFE (95:5) (repeated once). The organic layers were combined, dried over a cotton plug and concentrated to dryness under vacuum. The residue was purified by flash chromatography (Hexane/EtOAc 8:2 to 5:5) to give tert-butyl 2-((4S)-7-fluoro-1-methyl-6-oxo-5,6-dihydro-4H-isoxazolo[5,4-c]pyrido[4,3-e]azepin-4-yl)acetate as a solid (45 mg). LC/MS m/z 348 [M+H]+.

Workup

  1. customat 0° C.
  2. customto produce an emulsion) at 0° C. for 45 min
  3. extractionThe product was extracted with CH2Cl2 (
  4. customdried over a cotton plug
  5. concentrationconcentrated to dryness under vacuum
  6. customThe residue was purified by flash chromatography (Hexane/EtOAc 8:2 to 5:5)

Sources & evidence

ORD record
ord-83a41f181e87496ba85b73a2178f9516
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

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