Water → Methyl 2-(4-(4'-(2-methyl-5-(trifluoromethyl)oxazole-4-carboxamido)-[1,1'-biphenyl]-4-yl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate

HRID 881733Notes

Reaction equation

[CH3:1][C:2]1[O:3][C:4]([C:25]([F:28])([F:27])[F:26])=[C:5]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13](B3OC(C)(C)C(C)(C)O3)=[CH:12][CH:11]=2)=[O:8])[N:6]=1.Br[C:30]1[CH:35]=[CH:34][C:33]([C:36]23[CH2:43][CH2:42][C:39]([CH2:44][C:45]([O:47][CH3:48])=[O:46])([CH2:40][CH2:41]2)[O:38][CH2:37]3)=[CH:32][CH:31]=1.O.[F-].[Cs+]>O1CCOCC1.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH3:1][C:2]1[O:3][C:4]([C:25]([F:26])([F:27])[F:28])=[C:5]([C:7]([NH:9][C:10]2[CH:11]=[CH:12][C:13]([C:30]3[CH:31]=[CH:32][C:33]([C:36]45[CH2:41][CH2:40][C:39]([CH2:44][C:45]([O:47][CH3:48])=[O:46])([CH2:42][CH2:43]4)[O:38][CH2:37]5)=[CH:34][CH:35]=3)=[CH:14][CH:15]=2)=[O:8])[N:6]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a mixture of 2-methyl-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-5-(trifluoromethyl)oxazole-4-carboxamide (300 mg, 0.757 mmol) and methyl 2-(4-(4-bromophenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate (257 mg, 0.757 mmol) in dioxane (3 ml) was added H2O (0.33 ml) at room temperature. CsF (345 mg, 2.272 mmol) and Pd(amphos)Cl2 (53.6 mg, 0.076 mmol) were added and the mixture was degassed several times before being heated to 90° C. for overnight. The reaction mixture was cooled to room temperature and directly purified by column chromatography to afford the title compound as white solid after drying (200 mg, 50% yield). LC/MS, ESI-MS(+): 529.0, RT: 1.52 (Condition E).

Workup

customthe mixture was degassed several times
temperatureThe reaction mixture was cooled to room temperature
customdirectly purified by column chromatography

Sources & evidence

ORD record: ord-64412e2ef876479b88d45b5caf1b701a
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993619B2

Reaction notes

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