Ethyl Acetate → tert-butyl 7-(1-(tert-butoxycarbonyl)-2-methyl-1H-benzo[d]imidazol-6-yl)-2,3-dihydrobenzo[f][1,4]oxazepine-4(5H)-carboxylate

HRID 241085Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([CH3:10])[N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:6]=2[CH:18]=1.[CH3:19][C:20]([O:23][C:24]([N:26]1[CH2:32][C:31]2[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][C:30]=2[O:29][CH2:28][CH2:27]1)=[O:25])([CH3:22])[CH3:21].C(N(C(C)C)CC)(C)C.C(OCC)(=O)C>O1CCOCC1.O.CCCCCC>[CH3:15][C:14]([O:13][C:11]([N:7]1[C:6]2[CH:18]=[C:2]([C:34]3[CH:35]=[CH:36][C:30]4[O:29][CH2:28][CH2:27][N:26]([C:24]([O:23][C:20]([CH3:21])([CH3:19])[CH3:22])=[O:25])[CH2:32][C:31]=4[CH:33]=3)[CH:3]=[CH:4][C:5]=2[N:9]=[C:8]1[CH3:10])=[O:12])([CH3:17])[CH3:16]

Participants

Conditions

Temperature: 90 °C

Procedure

A suspension of 1,1-dimethylethyl 6-bromo-2-methyl-1H-benzimidazole-1-carboxylate (11.3 g, 36 mmol), (4-{[(1,1-dimethylethyl)oxy]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid (11.7 g, 40 mmol), dichloro[1,1-bis(diphenyl-phosphino]ferrocenepalladium (II) dichloromethane adduct (3.0 g, 10 mol %) in dioxane (115 mL) and water (28.5 mL) was degassed with nitrogen, and then diisopropylethylamine (18.6 g, 144 mmol) was added. The reaction mixture was stirred at 90° C. for 220 min, cooled to room temperature, and concentrated. Column chromatography on silica of the residue (gradient 25-30% ethyl acetate in hexane) afforded 1,1-dimethylethyl 7-(1-{[(1,1-dimethylethyl)oxy]carbonyl}-2-methyl-1H-benzimidazol-6-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (13.2 g, 76% yield) as an amorphous solid. MS (EI) for C27H33N3O5: 480 (MH+).

Workup

customwas degassed with nitrogen
temperaturecooled to room temperature
concentrationconcentrated

Sources & evidence

ORD record: ord-886e547f45184c799866d5b348068b35
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08648066B2

Reaction notes

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