Lithium Hydroxide → 4-(4-{[(1,1-Dimethylethyl)oxy]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)benzoic acid

HRID 473921Notes

Reaction equation

C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][C:14]3[O:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16][C:15]=3[CH:28]=2)=[CH:7][CH:6]=1)=[O:4].[OH-].[Li+]>O1CCCC1.O>[CH3:27][C:24]([O:23][C:21]([N:17]1[CH2:16][C:15]2[CH:28]=[C:11]([C:8]3[CH:7]=[CH:6][C:5]([C:3]([OH:4])=[O:2])=[CH:10][CH:9]=3)[CH:12]=[CH:13][C:14]=2[O:20][CH2:19][CH2:18]1)=[O:22])([CH3:25])[CH3:26]

Participants

Conditions

Temperature: 60 °C

Procedure

To a slurry of 1,1-dimethylethyl 7-{4-[(methyloxy)carbonyl]phenyl}-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (9.8 g, 26 mmol) in tetrahydrofuran (40 mL) was added a solution of lithium hydroxide (3.1 g, 130 mmol) in water (15 mL). The resulting mixture was heated at 60° C. for 18 h then partitioned between ethyl acetate (100 mL) and 1M hydrochloric acid (50 mL). The organic layer was washed with brine (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated. Purification by silica gel column chromatography (5% methanol in dichloromethane) provided 4-(4-{[(1,1-dimethylethyl)oxy]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)benzoic acid (8.1 g, 85% yield). MS (EI) for C21H23NO5: 370 (MH+).

Workup

customthen partitioned between ethyl acetate (100 mL) and 1M hydrochloric acid (50 mL)
washThe organic layer was washed with brine (50 mL)
dry with materialdried over anhydrous magnesium sulfate
filtrationfiltered
concentrationconcentrated
customPurification by silica gel column chromatography (5% methanol in dichloromethane)

Sources & evidence

ORD record: ord-61d27ab364bc4a94a43d630ed7eea382
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637499B2

Reaction notes

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