Ethyl Acetate → HCID 10319217, compound

HRID 1988929Notes

Reaction equation

HRID 1988929 reaction equation
Br[C:2]1[CH:17]=[CH:16][C:5]2[C:6]([C:9]([NH:11][CH2:12][CH:13]3[CH2:15][CH2:14]3)=[O:10])=[N:7][O:8][C:4]=2[CH:3]=1.[CH:18]1([NH:21][C:22](=[O:40])[C:23]2[CH:28]=[C:27](B3OC(C)(C)C(C)(C)O3)[C:26]([CH3:38])=[C:25]([F:39])[CH:24]=2)[CH2:20][CH2:19]1.C(=O)([O-])O.[Na+].C(OCC)(=O)C>C(O)(C)C.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>[CH:18]1([NH:21][C:22]([C:23]2[CH:24]=[C:25]([F:39])[C:26]([CH3:38])=[C:27]([C:2]3[CH:17]=[CH:16][C:5]4[C:6]([C:9]([NH:11][CH2:12][CH:13]5[CH2:15][CH2:14]5)=[O:10])=[N:7][O:8][C:4]=4[CH:3]=3)[CH:28]=2)=[O:40])[CH2:20][CH2:19]1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide2×HCID 586564981,2-Benzisoxazole-3-carboxamide, 6-bromo-N-(cyclopropylmethyl)-2×

Product 1

HCID 10319217HCID 10319217, compoundYield 78.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

A mixture of 6-bromo-N-(cyclopropylmethyl)-1,2-benzisoxazole-3-carboxamide (Intermediate 56) (0.03 g) N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (Intermediate 62) (0.03 g) saturated aqueous sodium hydrogen carbonate (0.25 ml) and tetrakis(triphenylphosphine)palladium(0) (1 mg) in isopropanol (0.5 ml) was stirred at reflux under nitrogen for 4 h. Ethyl acetate (2 ml) and water (2 ml) were added, the phases were separated and the aqueous layer was re-extracted with ethyl acetate. The combined organic extracts were washed with brine, dried using a hydrophobic filter tube and concentrated under a stream of nitrogen. The residue was purified on Varian Bond-Elut SPE cartridge (silica, 1 g) eluting with cyclohexane:ethyl acetate (100:0 to 50:50) to give the title compound as a colourless foam (0.03 g).

Workup

  1. temperatureat reflux under nitrogen for 4 h
  2. customthe phases were separated
  3. extractionthe aqueous layer was re-extracted with ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. customdried
  6. concentrationconcentrated under a stream of nitrogen
  7. customThe residue was purified on Varian Bond-Elut SPE cartridge (silica, 1 g)
  8. washeluting with cyclohexane:ethyl acetate (100:0 to 50:50)

Sources & evidence

ORD record
ord-9c964a75b6864ac59c9bcf778a3a76f6
Source dataset
uspto-grants-2010_01
Patent number
US07642276B2

Reaction notes

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