Phosphorus oxychloride → 2-chloro-N-(4-(5-methyl-4-phenyloxazol-2-yl)phenyl)benzamide

HRID 1951584Notes

Reaction equation

HRID 1951584 reaction equation
[Cl:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([NH:15][CH:16]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17](=O)[CH3:18])=[O:14])=[CH:9][CH:8]=1)=[O:5].P(Cl)(Cl)(Cl)=O.C(=O)(O)[O-].[Na+]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[O:14][C:17]([CH3:18])=[C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:15]=2)=[CH:11][CH:12]=1)=[O:5]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 574653752-chloro-N-(4-(((2-oxo-1-phenylpropyl)amino)carbonyl)phenyl)benzamide

Product 1

HCID 445483742-chloro-N-(4-(5-methyl-4-phenyloxazol-2-yl)phenyl)benzamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

a solution of 2-chloro-N-(4-(((2-oxo-1-phenylpropyl)amino)carbonyl)phenyl)benzamide (90 mg, 221 μmol) and phosphoryl trichloride (1.5 mL, 16093 μmol) in 2 mL pyridine was heated in a 70° C. oil bath. After 2 hours the reaction was poured into 10 mL saturated aqueous sodium bicarbonate solution and stirred vigorously for 30 minutes. The aqueous mixture was extracted with 25 mL ethyl acetate. The organic extract was washed with 10 mL each water then brine. The organic layer was stirred over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to afford a yellow-green oil. TLC indicated a very complex mixture of products. The crude product was purified by reversed-phase preparative HPLC to afford a colorless film (4 mg, 5%). ESI+ m/z=389.0 [MH]+.

Workup

  1. extractionThe aqueous mixture was extracted with 25 mL ethyl acetate
  2. extractionThe organic extract
  3. washwas washed with 10 mL each water
  4. stirringThe organic layer was stirred over magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customto afford a yellow-green oil
  8. additiona very complex mixture of products
  9. customThe crude product was purified by reversed-phase preparative HPLC
  10. customto afford a colorless film (4 mg, 5%)

Sources & evidence

ORD record
ord-064d8132b5464cda8017ca6cf7432b22
Source dataset
uspto-grants-2013_03
Patent number
US08404722B2

Reaction notes

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