Oxalyl chloride → 3-Methyl-2-oxo-1,3-benzoxazole-5-carbonyl chloride

HRID 2386873Notes

Reaction equation

HRID 2386873 reaction equation
[CH3:1][N:2]1[C:6]2[CH:7]=[C:8]([C:11](O)=[O:12])[CH:9]=[CH:10][C:5]=2[O:4][C:3]1=[O:14].C(Cl)(=O)C([Cl:18])=O>C(Cl)Cl.CN(C=O)C>[CH3:1][N:2]1[C:6]2[CH:7]=[C:8]([C:11]([Cl:18])=[O:12])[CH:9]=[CH:10][C:5]=2[O:4][C:3]1=[O:14]

Participants

5

Reactant 2

HCID 65578Oxalyl chlorideHCID 99901743-Methyl-2-oxo-2,3-dihydro-1,3-benzoxazole-5-carboxylic acid

Product 1

HCID 104431423-Methyl-2-oxo-1,3-benzoxazole-5-carbonyl chloride

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3-methyl-2-oxo-2,3-dihydro-benzooxazole-5-carboxylic acid (935 mg, obtained in Example 116, step 5) in CH2Cl2 (15 mL) were added two drops of DMF and oxalylchloride (0.66 mL). The mixture was stirred at room temperature for 1 hour and was then concentrated to dryness. 1,2-Dimethoxyethane (20 mL) was added and the solvent was evaporated again. The resulting solid was dried at high vacuum over night to give the crude acid chloride (3-methyl-2-oxo-2,3-dihydro-benzooxazole-5-carbonyl chloride). To a suspension of zinc powder (633 mg) in 1,2-dimethoxyethane (10 mL) was added tetrakis(triphenyl-phosphine)palladium(0) (56 mg). A suspension of the acid chloride in 1,2-dimethoxyethane (10 mL) was added. The mixture was cooled in an ice bath and a solution of 4-bromo-1-bromomethyl-2-trifluoromethyl-benzene (1.54 g, [CAS Reg. No. 335013-18-8]) in 1,2-dimethoxyethane (10 mL) was slowly added over a period of 15 minutes. The mixture was stirred for 10 minutes at 0° C. and then for 18 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. The residue was purified by flash chromatography (silica gel, heptane:ethyl acetate=1:1) to give the title compound as a yellow oil (944 mg, 47%). MS (neg. ion, m/e)=414.1 [(M−H)−].

Workup

  1. concentrationwas then concentrated to dryness
  2. addition1,2-Dimethoxyethane (20 mL) was added
  3. customthe solvent was evaporated again
  4. customThe resulting solid was dried at high vacuum over night

Sources & evidence

ORD record
ord-dd1f4768d5a841559ee0d1d7f2812df5
Source dataset
uspto-grants-2012_09
Patent number
US08268820B2

Reaction notes

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