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

HRID 881735Notes

Reaction equation

[CH2:1]([C:3]1[O:4][C:5]([C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:13]=2)=[O:10])=[C:6]([CH3:8])[N:7]=1)[CH3:2].Br[C:28]1[CH:33]=[CH:32][C:31]([C:34]23[CH2:41][CH2:40][C:37]([CH2:42][C:43]([O:45][CH3:46])=[O:44])([CH2:38][CH2:39]2)[O:36][CH2:35]3)=[CH:30][CH:29]=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>[CH2:1]([C:3]1[O:4][C:5]([C:9]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([C:28]3[CH:29]=[CH:30][C:31]([C:34]45[CH2:39][CH2:38][C:37]([CH2:42][C:43]([O:45][CH3:46])=[O:44])([CH2:40][CH2:41]4)[O:36][CH2:35]5)=[CH:32][CH:33]=3)=[CH:16][CH:17]=2)=[O:10])=[C:6]([CH3:8])[N:7]=1)[CH3:2]

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 2-ethyl-4-methyl-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazole-5-carboxamide (200 mg, 0.561 mmol) and methyl 2-(4-(4-bromophenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate (190 mg, 0.561 mmol) in dioxane (3 ml) was added H2O (0.33 ml). CsF (256 mg, 1.684 mmol) and Pd(amphos)Cl2 (39.8 mg, 0.056 mmol) were then added and the mixture was degassed before being heated at 90° C. for overnight. The reaction mixture was then cooled to room temperature and directly purified by column chromatography to afford the title compound as white solid after drying (159 mg, 58% yield). LC/MS, ESI-MS(+): 489.0, RT: 1.40 (Condition E).

Workup

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

Sources & evidence

ORD record: ord-70f9ecb5f4e2449cb0ad6a3cb5142a91
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993619B2

Reaction notes

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