1,4-Dioxane → 1,1-dimethylethyl 7-(4-amino-3-nitrophenyl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

HRID 473866Notes

Reaction equation

HRID 473866 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:14][C:13]2[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][C:12]=2[O:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3].Br[C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[C:25]([N+:30]([O-:32])=[O:31])[CH:24]=1.O1CCOCC1.CCN(C(C)C)C(C)C>O>[NH2:27][C:26]1[CH:28]=[CH:29][C:23]([C:16]2[CH:17]=[CH:18][C:12]3[O:11][CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:4])([CH3:3])[CH3:1])=[O:7])[CH2:14][C:13]=3[CH:15]=2)=[CH:24][C:25]=1[N+:30]([O-:32])=[O:31]

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 701324-Bromo-2-nitroanilineHCID 81531DiisopropylethylamineHCID 59604707(4-(Tert-butoxycarbonyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepin-7-yl)boronic acid

Product 1

HCID 675056591,1-dimethylethyl 7-(4-amino-3-nitrophenyl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylateYield 72.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

(4-{[(1,1-dimethylethyl)oxycarbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid (example 1, step 2) (2.22 g, 7.57 mmol) and 4-bromo-2-nitroaniline (1.56 g, 7.20 mmol) were taken into dioxane (20 mL), water (4 mL) and DIPEA (5.4 mL, 31 mmol) followed by addition of dichloro[1,1-bis(diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (322 mg, 0.39 mmol) and the mixture was heated to 95° C. for 2 h. The mixture was cooled to room temperature and partitioned with ethyl acetate and 10% aqueous citric acid. The biphasic mixture was filtered through a celite pad and the organic filtrate was washed once with 0.5M aqueous hydrochloric acid, brine then dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography to give 1,1-dimethylethyl 7-(4-amino-3-nitrophenyl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (2.01 g, 69% yield) as a yellow crystalline solid.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned with ethyl acetate and 10% aqueous citric acid
  3. filtrationThe biphasic mixture was filtered through a celite pad
  4. washthe organic filtrate was washed once with 0.5M aqueous hydrochloric acid, brine
  5. dry with materialthen dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-b6f0056e96de490e9cea155ea9f9a963
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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