Potassium Iodide → 7-(4-Methoxycarbonyl-benzyloxy)-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid tert-butyl ester

HRID 645782Notes

Reaction equation

HRID 645782 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[CH:15]=[C:16]([OH:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Br[CH2:29][C:30]1[CH:39]=[CH:38][C:33]([C:34]([O:36][CH3:37])=[O:35])=[CH:32][CH:31]=1>CC(=O)CC>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[CH:15]=[C:16]([O:19][CH2:29][C:30]3[CH:31]=[CH:32][C:33]([C:34]([O:36][CH3:37])=[O:35])=[CH:38][CH:39]=3)[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 256687Methyl 4-(bromomethyl)benzoateHCID 18173274tert-butyl 7-hydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine-3-carboxylate

Product 1

HCID 592579207-(4-Methoxycarbonyl-benzyloxy)-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent2×

Procedure

7-Hydroxy-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid tert-butyl ester (WO 02/40471) (5.27 g, 20.0 mmol), potassium carbonate (8.30 g, 60.0 mmol) and catalytic potassium iodide were suspended in butanone (100 ml). Methyl 4-(bromomethyl)benzoate (5.5 g, 24.0 mmol) dissolved in butanone (50 ml) was added dropwise after which the reaction mixture was stirred at reflux for 24 hours. The reaction mixture was cooled, the solids were filtered and then washed with acetone. The filtrate was concentrated in vacuo and the crude mixture was purified by column chromatography eluting with a mixture of ethyl acetate:hexane (1:4) to afford the title compound (D3). MS (ES+) m/e 344 [(M+H)—CO2tBu]+.

Workup

  1. additionwas added dropwise after which the reaction mixture
  2. temperatureat reflux for 24 hours
  3. temperatureThe reaction mixture was cooled
  4. filtrationthe solids were filtered
  5. washwashed with acetone
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe crude mixture was purified by column chromatography
  8. washeluting with a mixture of ethyl acetate:hexane (1:4)

Sources & evidence

ORD record
ord-892f8232c491487d849a0ee39fe65016
Source dataset
uspto-grants-2010_04
Patent number
US07704994B2

Reaction notes

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