Potassium Iodide → tert-butyl 7-(benzyloxy)-1,2,4,5-tetrahydro-3H-benzo[d]azepine-3-carboxylate

HRID 222647Notes

Reaction equation

HRID 222647 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+].[CH2:28](Br)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=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][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=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 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 18173274tert-butyl 7-hydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine-3-carboxylate

Product 1

HCID 57437616tert-butyl 7-(benzyloxy)-1,2,4,5-tetrahydro-3H-benzo[d]azepine-3-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Procedure

7-Hydroxy-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid tert-butyl ester (PCT Int. Appl. (2002), WO 02/40471) (790 mg, 3 mmol), potassium carbonate (1.24 g, 9 mmol) and catalytic potassium iodide were suspended in 2-butanone (20 ml). Benzyl bromide (536 μL, 4.5 mmol) was added and the mixture heated at reflux for 24 hours. The solids were filtered and then washed with acetone. The filtrate was concentrated in vacuo and the crude oil purified by column chromatography, eluting with a mixture of ethyl acetate and hexane (1:4) to afford the title compound (D1) (1.06 g, 100%), 1H NMR (CDCl3) 7.44 (5H, m), 7.03 (1H, d, J 8.1 Hz), 6.77 (1H, s), 6.74 (1H, dd, J 8.1 & 2.4 Hz), 3.49 (4H, m), 2.84 (4H, m), 1.48 (9H, s).

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 24 hours
  3. filtrationThe solids were filtered
  4. washwashed with acetone
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe crude oil purified by column chromatography
  7. washeluting with a mixture of ethyl acetate and hexane (1:4)

Sources & evidence

ORD record
ord-c237a66c16a2439988fe289127dc41d2
Source dataset
uspto-grants-2012_06
Patent number
US08207331B2

Reaction notes

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