Dichloromethane → 1,1-dimethylethyl 7-[4-(1-{[(2-methylpropyl)oxy]carbonyl}-1H-imidazol-2-yl)phenyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

HRID 473906Notes

Reaction equation

HRID 473906 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([C:13]([O:15][CH2:16][CH:17]([CH3:19])[CH3:18])=[O:14])[CH:10]=[CH:11][N:12]=2)=[CH:4][CH:3]=1.[CH3:20][C:21]([O:24][C:25]([N:27]1[CH2:33][C:32]2[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][C:31]=2[O:30][CH2:29][CH2:28]1)=[O:26])([CH3:23])[CH3:22].C(N(C(C)C)CC)(C)C.ClCCl>O1CCOCC1.C(OCC)(=O)C>[CH3:18][CH:17]([CH3:19])[CH2:16][O:15][C:13]([N:9]1[CH:10]=[CH:11][N:12]=[C:8]1[C:5]1[CH:6]=[CH:7][C:2]([C:35]2[CH:36]=[CH:37][C:31]3[O:30][CH2:29][CH2:28][N:27]([C:25]([O:24][C:21]([CH3:22])([CH3:20])[CH3:23])=[O:26])[CH2:33][C:32]=3[CH:34]=2)=[CH:3][CH:4]=1)=[O:14]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 59604707(4-(Tert-butoxycarbonyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepin-7-yl)boronic acidHCID 66820246isobutyl 2-(4-bromophenyl)-1H-imidazole-1-carboxylate

Product 1

HCID 675140761,1-dimethylethyl 7-[4-(1-{[(2-methylpropyl)oxy]carbonyl}-1H-imidazol-2-yl)phenyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylateYield 43%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of isobutyl 2-(4-bromophenyl)-1H-imidazole-1-carboxylate (example 4, step 5) (0.50 g, 1.55 mmol), (4-{[(1,1-dimethylethyl)oxy]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid (example 1, step 2) (0.63 g, 1.70 mmol) and diisopropyethylamine (1.50 mL, 8.50 mmol) in 20% aqueous 1,4-dioxane (10 mL) was deoxygenated for five minutes by bubbling nitrogen gas into it, followed by the addition of 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) complex with dichloromethane (70 mg, 0.085 mmol). The reaction mixture was heated to 80° C. for 2 hours. On cooling to room temperature the mixture was diluted with ethyl acetate (250 mL) then filtered through a pad of Celite. The organic filtrate was washed with 10% aqueous citric acid (50 mL), brine then dried over anhydrous sodium sulfate, filtered and concentrated. Silica gel column chromatography (hexane-ethyl acetate 9:1 to 7:3) provided 1,1-dimethylethyl 7-[4-(1-{[(2-methylpropyl)oxy]carbonyl}-1H-imidazol-2-yl)phenyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (0.32 g. 43%). 1H NMR (400 MHz, d6-DMSO): 7.73 (d, 1H), 7.67 (s, 4H), 7.56 (m, 2H), 7.14 (d, 1H), 7.08 (m, 1H), 4.56 (br s, 1H), 4.51 (br s, 2H), 4.13 (br s, 1H), 4.08 (m, 2H), 3.74 (m, 2H), 1.86 (m, 1H), 1.34 (s, 1H), 1.32 (s, 9H), 0.77 (d, 6H). MS (EI) for C28H33N3O5: 492 (MH+).

Workup

  1. customby bubbling nitrogen gas into it
  2. temperatureOn cooling to room temperature the mixture
  3. filtrationthen filtered through a pad of Celite
  4. washThe organic filtrate was washed with 10% aqueous citric acid (50 mL), brine
  5. dry with materialthen dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-80fb1bde78ae471a96796c964ad10616
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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