Cyclopropylboronic acid → HCID 68227816, compound

HRID 1027598Notes

Reaction equation

HRID 1027598 reaction equation
[CH:1]1(B(O)O)[CH2:3][CH2:2]1.C[O:8][C:9](=[O:34])[C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH2:20][C:19]([C:25]3[CH:30]=[C:29]([Cl:31])[CH:28]=[C:27]([Cl:32])[CH:26]=3)([C:21]([F:24])([F:23])[F:22])[O:18][N:17]=2)=[CH:12][C:11]=1Br>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C>[CH:1]1([C:11]2[CH:12]=[C:13]([C:16]3[CH2:20][C:19]([C:25]4[CH:26]=[C:27]([Cl:32])[CH:28]=[C:29]([Cl:31])[CH:30]=4)([C:21]([F:24])([F:22])[F:23])[O:18][N:17]=3)[CH:14]=[CH:15][C:10]=2[C:9]([OH:34])=[O:8])[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 2760897Cyclopropylboronic acidHCID 59563492HCID 59563492, compound

Product 1

HCID 68227816HCID 68227816, compoundYield 93.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of cyclopropyl boronic acid (0.67 g), 2-bromo-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoic acid methyl ester (3 g) and Bis(triphenylphosphine)palladium(II) chloride (210 mg) were sequentially added to degassed toluene (38 ml). The reaction mixture was stirred for 30 min at room temperature then a degassed aqueous 2N solution of potassium phosphate (7 ml) was added and the resulting mixture was heated at 110° C. overnight. The reaction mixture was filtered over Hyflo and the resulting solution was concentrated in vacuo to give a yellow oil, which was poured into ethyl acetate. The organic phase was washed with water, dried over sodium sulfate, and the solvents were evaporated in vacuo. The product was used as such for the saponification step, as described in Example 17, Step E to afford the title acid compound (2.5 g) as a yellow solid. LCMS (Method F) 2.15 min M−H 442/444.

Workup

  1. customto degassed toluene (38 ml)
  2. additiona degassed aqueous 2N solution of potassium phosphate (7 ml) was added
  3. temperaturethe resulting mixture was heated at 110° C. overnight
  4. filtrationThe reaction mixture was filtered over Hyflo
  5. concentrationthe resulting solution was concentrated in vacuo
  6. customto give a yellow oil, which
  7. washThe organic phase was washed with water
  8. dry with materialdried over sodium sulfate
  9. customthe solvents were evaporated in vacuo

Sources & evidence

ORD record
ord-424d4dc3007f4fc98566e5361f1f6f60
Source dataset
uspto-grants-2014_05
Patent number
US08735362B2

Reaction notes

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