Hydrochloric Acid → Methyl 5-benzyloxy-4-methoxy-2-(5-methyl-[1,2,4]oxadiazol-3-yl)benzoate

HRID 2075960Notes

Reaction equation

HRID 2075960 reaction equation
CN(C)C=O.[CH2:6]([O:13][C:14]1[C:19]([O:20][CH3:21])=[CH:18][C:17]([C:22]2[N:26]=[C:25]([CH3:27])[O:24][N:23]=2)=[C:16](I)[CH:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C]=O.Cl.[C:32]([O:35][CH2:36]C)(=[O:34])C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(N(CC)CC)C.CO>[CH2:6]([O:13][C:14]1[C:19]([O:20][CH3:21])=[CH:18][C:17]([C:22]2[N:26]=[C:25]([CH3:27])[O:24][N:23]=2)=[C:16]([CH:15]=1)[C:32]([O:35][CH3:36])=[O:34])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 508988613-(4-Benzyloxy-2-iodo-5-methoxyphenyl)-5-methyl-[1,2,4]oxa-diazoleHCID 178418416HCID 178418416, compound

Product 1

HCID 50899157Methyl 5-benzyloxy-4-methoxy-2-(5-methyl-[1,2,4]oxadiazol-3-yl)benzoate

Reagents, catalysts & solvents 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of tris(dibenzylideneacetone)dipalladium (0) (163 mg), 1,1′-bis(diphenylphosphino)ferrocene (394 mg) and N,N-dimethylformamide (10 mL) was stirred under an argon atmosphere for 10 minutes. 3-(4-Benzyloxy-2-iodo-5-methoxy-phenyl)-5-methyl-[1,2,4]oxadiazole (reference example 4-1) (1.5 g), methanol (15 mL) and triethylamine (1.5 mL) were added to the mixture. After displacement to a carbon monoxide atmosphere, the mixture was stirred at 90° C. for 16 hours. After cooling to room temperature, ethyl acetate and 2 mol/L hydrochloric acid were added to the mixture. The separated organic layer was washed with water, a 2 mol/L aqueous solution of sodium hydroxide, an aqueous solution of sodium bicarbonate and brine successively, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: 15%-30% ethyl acetate/hexane, gradient elution) to give the title compound (1.1 g).

Workup

  1. washThe separated organic layer was washed with water
  2. dry with materiala 2 mol/L aqueous solution of sodium hydroxide, an aqueous solution of sodium bicarbonate and brine successively, dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (eluent: 15%-30% ethyl acetate/hexane, gradient elution)

Sources & evidence

ORD record
ord-4394d30b80e24c39a983e941e61c884f
Source dataset
uspto-grants-2011_04
Patent number
US07923462B2

Reaction notes

Loading…