Ethyl Acetate → 7-(3-fluoro-4-(trifluoromethyl)phenyl)-4-(pyrimidin-2-ylmethyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one

HRID 717048Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]([CH2:12][C:13]3[N:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[C:7](=[O:19])[C:6]=2[CH:20]=1.[F:21][C:22]1[CH:23]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:25]=[CH:26][C:27]=1[C:28]([F:31])([F:30])[F:29].C(=O)([O-])[O-].[Cs+].[Cs+].CCOC(C)=O>CN(C=O)C.O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[F:21][C:22]1[CH:23]=[C:24]([C:2]2[CH:3]=[CH:4][C:5]3[O:11][CH2:10][CH2:9][N:8]([CH2:12][C:13]4[N:18]=[CH:17][CH:16]=[CH:15][N:14]=4)[C:7](=[O:19])[C:6]=3[CH:20]=2)[CH:25]=[CH:26][C:27]=1[C:28]([F:29])([F:30])[F:31]

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of 7-bromo-4-(pyrimidin-2-ylmethyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one (50 mg, 0.15 mmol), 2-(3-fluoro-4-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (52 mg, 0.18 mmol), cesium carbonate (146 mg, 0.45 mmol), 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (10 mg, 0.015 mmol) was dissolved in a degassed mixture of DMF and water 3/1.5 (4.5 mL). The mixture was heated in microwave at 85° C. for 40 min. The mixture was poured into EtOAc and washed with water and brine. The organic layer was collected, dried over sodium sulfate and loaded onto silica gel. A flash column (5% MeOH in EtOAc) and reverse phase chromatography gave 7-(3-fluoro-4-(trifluoromethyl)phenyl)-4-(pyrimidin-2-ylmethyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5 (2H)-one.

Workup

washwashed with water and brine
customThe organic layer was collected
dry with materialdried over sodium sulfate

Sources & evidence

ORD record: ord-c2eec6f3534a40868a865c6c3b45ed1e
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193694B2

Reaction notes

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