Diisopropylethylamine → 1,1-dimethylethyl 7-(4-{[(2,2-difluoroethyl)amino]carbonyl}phenyl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

HRID 473923Notes

Reaction equation

HRID 473923 reaction equation
Cl[C:2]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[CH:12][C:13]3[O:19][CH2:18][CH2:17][N:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:15][C:14]=3[CH:27]=2)=[CH:6][CH:5]=1)=[O:3].CCN(C(C)C)C(C)C.[F:37][CH:38]([F:41])[CH2:39][NH2:40]>O1CCCC1>[F:37][CH:38]([F:41])[CH2:39][NH:40][C:2]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[CH:12][C:13]3[O:19][CH2:18][CH2:17][N:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:15][C:14]=3[CH:27]=2)=[CH:6][CH:5]=1)=[O:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1362742,2-DifluoroethanamineHCID 866720391,1-dimethylethyl 7-[4-(chlorocarbonyl)phenyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

Product 1

HCID 866720401,1-dimethylethyl 7-(4-{[(2,2-difluoroethyl)amino]carbonyl}phenyl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylateYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1,1-dimethylethyl 7-[4-(chlorocarbonyl)phenyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (1.0 g, 2.6 mmol) and DIPEA (2.2 mL, 13 mmol) in tetrahydrofuran (10 mL) was added 2,2-difluoroethylamine (0.21 g, 2.6 mmol). The reaction mixture was stirred for 2 h and then partitioned between ethyl acetate (20 mL) and 1M hydrochloric acid (20 mL). The organic layer was washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated. Purification by column chromatography on silica (30% ethyl acetate in hexanes) provided 1,1-dimethylethyl 7-(4-{[(2,2-difluoroethyl)amino]carbonyl}phenyl)-2,3-dihydro-1,4-benzoxazepine-4 (5H)-carboxylate (0.95 g, 85% yield). MS (EI) for C23H26F2N2O4: 433 (MH1).

Workup

  1. custompartitioned between ethyl acetate (20 mL) and 1M hydrochloric acid (20 mL)
  2. washThe organic layer was washed with brine (20 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by column chromatography on silica (30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a43e3da71e7f4874aab10e7ddac41c3d
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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