1,2-Dimethoxyethane → Ethyl 5-(2,5-difluorobenzyl)isoxazole-3-carboxylate

HRID 1918558Notes

Reaction equation

HRID 1918558 reaction equation
COCCOC.Br[CH2:8][C:9]1[O:13][N:12]=[C:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:10]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>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.O>[F:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=1[CH2:8][C:9]1[O:13][N:12]=[C:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:10]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 2734335(2,5-Difluorophenyl)boronic acidHCID 13124955Ethyl 5-(bromomethyl)-1,2-oxazole-3-carboxylate

Product 1

HCID 66831915Ethyl 5-(2,5-difluorobenzyl)isoxazole-3-carboxylateYield 59%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

1,2-Dimethoxyethane (8 mL) and water (2 mL) were added to the mixture of ethyl 5-(bromomethyl)isoxazole-3-carboxylate (1.00 g; 4.27 mmol), 2,5-difluorophenylboronic acid (0.773 g; 4.70 mmol), tetrakis(triphenylphosphine)palladium(0) (0.248 g; 0.640 mmol) and sodium carbonate (0.911 g; 8.55 mmol). The mixture was irradiated in a microwave oven at 130° C. for 20 minutes. After cooling, the reaction mixture was extracted with ethyl acetate and water. The organic layer was concentrated under reduced pressure and the residue was purified by flash chromatography on silica gel (eluent: 5 to 40% of ethyl acetate in heptane) to give 0.67 g (59%) of ethyl 5-(2,5-difluorobenzyl)isoxazole-3-carboxylate as a yellow oil.

Workup

  1. customThe mixture was irradiated in a microwave oven at 130° C. for 20 minutes
  2. temperatureAfter cooling
  3. extractionthe reaction mixture was extracted with ethyl acetate and water
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. customthe residue was purified by flash chromatography on silica gel (eluent: 5 to 40% of ethyl acetate in heptane)

Sources & evidence

ORD record
ord-9801bf5490884015ae1f168f8ad3998b
Source dataset
uspto-grants-2013_12
Patent number
US08618138B2

Reaction notes

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