Sodium Carbonate → 1,1-dimethylethyl 7-{5-acetyl-2-[(2-pyrazinylmethyl)oxy]phenyl}-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate

HRID 879995

Reaction equation

HRID 879995 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:16](=[O:18])[CH3:17])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[N:14][CH:13]=[CH:12][N:11]=1.CC1(C)C(C)(C)OB([C:27]2[CH:44]=[CH:43][C:30]3[CH2:31][CH2:32][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:34][CH2:35][C:29]=3[CH:28]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC>[C:16]([C:4]1[CH:5]=[CH:6][C:7]([O:8][CH2:9][C:10]2[CH:15]=[N:14][CH:13]=[CH:12][N:11]=2)=[C:2]([C:27]2[CH:44]=[CH:43][C:30]3[CH2:31][CH2:32][N:33]([C:36]([O:38][C:39]([CH3:40])([CH3:41])[CH3:42])=[O:37])[CH2:34][CH2:35][C:29]=3[CH:28]=2)[CH:3]=1)(=[O:18])[CH3:17]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 57505869tert-Butyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,4,5-tetrahydro-3H-benzo[d]azepine-3-carboxylateHCID 706653921-{3-Bromo-4-[(2-pyrazinylmethyl)oxy]phenyl}ethanone

Product 1

HCID 706651151,1-dimethylethyl 7-{5-acetyl-2-[(2-pyrazinylmethyl)oxy]phenyl}-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylateYield 30%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a stirred solution of 1-{3-bromo-4-[(2-pyrazinylmethyl)oxy]phenyl}ethanone (0.2 g) and 1,1-dimethylethyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (0.34 g) in DME (4 ml) was added aqueous sodium carbonate (2M, 0.98 ml). This was degassed with nitrogen for 15 min before adding Tetrakis (37 mg). The reaction was heated under reflux overnight. TLC indicated the reaction had gone to completion and so it was cooled, diluted with water and extracted with ethyl acetate. The combined organics were dried over sodium sulphate and concentrated in vacuo to yield a crude product which was purified by column chromatography, eluting with 0-18% ethyl acetate in hexane. The appropriate fractions were concentrated in vacuo to yield the title compound, 0.093 g, 30% yield.

Workup

  1. customThis was degassed with nitrogen for 15 min
  2. additionbefore adding Tetrakis (37 mg)
  3. temperatureThe reaction was heated
  4. temperatureunder reflux overnight
  5. temperaturewas cooled
  6. additiondiluted with water
  7. extractionextracted with ethyl acetate
  8. dry with materialThe combined organics were dried over sodium sulphate
  9. concentrationconcentrated in vacuo
  10. customto yield a crude product which
  11. customwas purified by column chromatography
  12. washeluting with 0-18% ethyl acetate in hexane
  13. concentrationThe appropriate fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-cd226a5b61254cfebbfc0560a470aab1
Source dataset
uspto-grants-2015_03
Patent number
US08993560B2

Linked notes

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