Oxalyl chloride → 5-[2-(4-Bromo-2-chloro-phenyl)-acetyl]-3-methyl-3H-benzooxazol-2-one

HRID 2386810Notes

Reaction equation

HRID 2386810 reaction equation
[CH3:1][N:2]1[C:6]2[CH:7]=[C:8]([C:11]([OH:13])=O)[CH:9]=[CH:10][C:5]=2[O:4][C:3]1=[O:14].C(Cl)(=O)C(Cl)=O.CN1C2C=C(C(Cl)=O)C=CC=2OC1=O.[Br:35][C:36]1[CH:41]=[CH:40][C:39]([CH2:42]Br)=[C:38]([Cl:44])[CH:37]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C.COCCOC.[Zn].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:35][C:36]1[CH:41]=[CH:40][C:39]([CH2:42][C:11]([C:8]2[CH:9]=[CH:10][C:5]3[O:4][C:3](=[O:14])[N:2]([CH3:1])[C:6]=3[CH:7]=2)=[O:13])=[C:38]([Cl:44])[CH:37]=1

Participants

11

Reactant 5

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 99901743-Methyl-2-oxo-2,3-dihydro-1,3-benzoxazole-5-carboxylic acidHCID 104431423-Methyl-2-oxo-1,3-benzoxazole-5-carbonyl chlorideHCID 219144864-Bromo-1-(bromomethyl)-2-chlorobenzene

Product 1

HCID 666970355-[2-(4-Bromo-2-chloro-phenyl)-acetyl]-3-methyl-3H-benzooxazol-2-one

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 23994ZincCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent3×

Procedure

To a suspension of 3-methyl-2-oxo-2,3-dihydro-benzooxazole-5-carboxylic acid (2.20 g) in CH2Cl2 (30 mL) were added five drops of DMF and oxalylchloride (1.57 mL). The mixture was stirred at room temperature for 1.5 hours and was then concentrated to dryness. 1,2-Dimethoxyethane (150 mL) was added and the solvent was evaporated again to give the crude acid chloride (3-methyl-2-oxo-2,3-dihydro-benzooxazole-5-carbonyl chloride). To a suspension of zinc powder (1.49 g) in 1,2-dimethoxyethane (15 mL) was added tetrakis(triphenylphosphine)palladium(0) (132 mg). A suspension of the acid chloride in 1,2-dimethoxyethane (20 mL) was added. The mixture was cooled in an ice bath and a solution of 4-bromo-1-bromomethyl-2-chloro-benzene (3.25 g, [CAS Reg. No. 89720-77-4]) in 1,2-dimethoxyethane (15 mL) was slowly added over a period of 30 minutes. The mixture was stirred for 10 minutes at 0° C. and then for 2 hours at r.t. The reaction mixture was poured into ice and basified with sat. NaHCO3. The aqueous phase was then extracted two times with ethyl acetate and the organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. Ethyl acetate (50 mL) was added to the resulting precipitate and the suspension was stirred for 30 minutes at r.t. The solid was filtered off and dried in vacuo. The title compound was obtained as a light yellow solid (1.95 g, 40%). MS (neg. ion, m/e)=378.0 [(M−H)−].

Workup

  1. concentrationwas then concentrated to dryness
  2. addition1,2-Dimethoxyethane (150 mL) was added
  3. customthe solvent was evaporated again
  4. customto give the crude acid chloride (3-methyl-2-oxo-2,3-dihydro-benzooxazole-5-carbonyl chloride)
  5. additionwas added
  6. temperatureThe mixture was cooled in an ice bath
  7. stirringThe mixture was stirred for 10 minutes at 0° C.
  8. waitfor 2 hours at r.t
  9. extractionThe aqueous phase was then extracted two times with ethyl acetate
  10. washthe organic layers were washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. customthe solvent was evaporated
  14. additionEthyl acetate (50 mL) was added to the resulting precipitate
  15. stirringthe suspension was stirred for 30 minutes at r.t
  16. filtrationThe solid was filtered off
  17. customdried in vacuo

Sources & evidence

ORD record
ord-54e78c6ae0224a4da9369378579b86fc
Source dataset
uspto-grants-2012_09
Patent number
US08268820B2

Reaction notes

Loading…