Water → 3-(Pyrimidin-2-ylmethoxy)-5-(4-(trifluoromethoxy)phenyl)benzo[d]isoxazole

HRID 1482865Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]2[O:9][N:8]=[C:7]([O:10][CH2:11][C:12]3[N:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[C:6]=2[CH:18]=1.[F:19][C:20]([F:32])([F:31])[O:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N:13]1[CH:14]=[CH:15][CH:16]=[N:17][C:12]=1[CH2:11][O:10][C:7]1[C:6]2[CH:18]=[C:2]([C:25]3[CH:24]=[CH:23][C:22]([O:21][C:20]([F:19])([F:31])[F:32])=[CH:27][CH:26]=3)[CH:3]=[CH:4][C:5]=2[O:9][N:8]=1

Participants

Conditions

Temperature: 80 °C

Procedure

5-Bromo-3-(pyrimidin-2-ylmethoxy)benzo[d]isoxazole (120 mg, 0.39 mmol), 4-(trifluoromethoxy)phenylboronic acid (120 mg, 0.58 mmol), potassium carbonate (500 mg), and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (25 mg, 0.034 mmol) were combined in 6 mL DMF. 3 mL water was added and the mixture was stirred at 80° C. for two hours. The reaction mixture was diluted with 60 mL ethyl acetate, washed with water and brine and evaporated under vacuum. Flash chromatographic purification on 12 g silica gel with 0-60% ethyl acetate in hexane gave 3-(pyrimidin-2-ylmethoxy)-5-(4-(trifluoromethoxy)phenyl)benzo[d]isoxazole (94 mg, 0.24 mmol).

Workup

washwashed with water and brine
customevaporated under vacuum
customFlash chromatographic purification on 12 g silica gel with 0-60% ethyl acetate in hexane

Sources & evidence

ORD record: ord-6dfb80fad55146fe8ab2a6bf9a0f441f
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09416115B2

Reaction notes

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