Potassium Carbonate → 2-(4-fluorophenyl)-1-({7-[4-(1H-imidazol-2-yl)phenyl]-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl}carbonyl)piperidin-4-one

HRID 473909Notes

Reaction equation

HRID 473909 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][C:12](=[O:14])[CH2:11][CH2:10][N:9]2[C:15]([N:17]2[CH2:23][C:22]3[CH:24]=[C:25]([C:28]4[CH:33]=[CH:32][C:31]([C:34]5[N:35](C(OCC(C)C)=O)[CH:36]=[CH:37][N:38]=5)=[CH:30][CH:29]=4)[CH:26]=[CH:27][C:21]=3[O:20][CH2:19][CH2:18]2)=[O:16])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+]>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][C:12](=[O:14])[CH2:11][CH2:10][N:9]2[C:15]([N:17]2[CH2:23][C:22]3[CH:24]=[C:25]([C:28]4[CH:33]=[CH:32][C:31]([C:34]5[NH:38][CH:37]=[CH:36][N:35]=5)=[CH:30][CH:29]=4)[CH:26]=[CH:27][C:21]=3[O:20][CH2:19][CH2:18]2)=[O:16])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 675151262-methylpropyl 2-[4-(4-{[2-(4-fluorophenyl)-4-oxopiperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)phenyl]-1H-imidazole-1-carboxylate

Product 1

HCID 498336822-(4-fluorophenyl)-1-({7-[4-(1H-imidazol-2-yl)phenyl]-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl}carbonyl)piperidin-4-oneYield 86%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2-methylpropyl 2-[4-(4-{[2-(4-fluorophenyl)-4-oxopiperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)phenyl]-1H-imidazole-1-carboxylate (0.27 g, 0.44 mmol) in methanol (50 mL) was added potassium carbonate (0.37 g, 2.65 mmol) at 0° C. and the reaction mixture was stirred for 2 hours at room temperature. The solid was filtered off and the pH of the resulting solution was adjusted to 6-7 by addition of glacial acetic acid. The solvent was evaporated and the residue was dissolved in ethyl acetate (250 mL), washed with saturated aqueous sodium bicarbonate (2×50 mL), brine and dried over anhydrous sodium sulfate, filtered and concentrated. The precipitating product was collected by filtration, washed with hexane and dried to give 2-(4-fluorophenyl)-1-({7-[4-(1H-imidazol-2-yl)phenyl]-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl}carbonyl)piperidin-4-one (0.19 g, 86%). 1H NMR (400 MHz, d6-DMSO): 12.48 (s, 1H), 8.00 (d, 2H), 7.68 (d, 2H), 7.61 (d, 1H), 7.55 (dd, 1H), 7.31-7.26 (m, 3H), 710-6.92 (m, 4H), 5.20 (t, 1H), 4.59 (s, 2H), 4.23 (m, 2H), 3.73-3.63 (m, 3H), 3.31 (m, 1H), 2.85 (m, 2H), 2.61 (m, 1H), 2.30 (2t, 1H). MS (EI) for C30H27FN4O3: 511 (MH+).

Workup

  1. filtrationThe solid was filtered off
  2. additionthe pH of the resulting solution was adjusted to 6-7 by addition of glacial acetic acid
  3. customThe solvent was evaporated
  4. dissolutionthe residue was dissolved in ethyl acetate (250 mL)
  5. washwashed with saturated aqueous sodium bicarbonate (2×50 mL), brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. filtrationThe precipitating product was collected by filtration
  10. washwashed with hexane
  11. customdried

Sources & evidence

ORD record
ord-fbc2c473e10042b3a954fd9bd8ea5ae5
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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