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

HRID 58571

Reaction equation

HRID 58571 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-56c06f3f570d491c85ebf3b41cfd0baa
Source dataset
uspto-grants-2016_09
Patent number
US09434722B2

Linked notes

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