Aluminum(III) Chloride → ethyl 9-bromo-7-chloro-4,5-dihydro-3H-benzofuro[2,3-d]azepine-3-carboxylate

HRID 2179429Notes

Reaction equation

HRID 2179429 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([Cl:25])[C:5]2[O:9][C:8]([CH2:10][CH2:11][N:12]([CH2:18][CH:19](OC)OC)[C:13](=[O:17])[O:14][CH2:15][CH3:16])=[CH:7][C:6]=2[CH:24]=1.[Al+3].[Cl-].[Cl-].[Cl-]>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([Cl:25])[C:5]2[O:9][C:8]3[CH2:10][CH2:11][N:12]([C:13]([O:14][CH2:15][CH3:16])=[O:17])[CH:18]=[CH:19][C:7]=3[C:6]=2[CH:24]=1

Participants

4

Reactant 2

HCID 6451240Aluminum(III) ChlorideHCID 68109872Ethyl 2-(5-bromo-7-chlorobenzofuran-2-yl)ethyl(2,2-dimethoxyethyl)carbamate

Product 1

HCID 68109610ethyl 9-bromo-7-chloro-4,5-dihydro-3H-benzofuro[2,3-d]azepine-3-carboxylateYield 9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of the product of step B (660 mg, 1.52 mmol) in anhydrous dichloromethane (8 mL) at 0° C. was added AlCl3 (810 mg, 6.07 mmol) and the reaction mixture was allowed to warm to ambient temperature over 3 h before being quenched by addition of aqueous sodium bicarbonate solution. The organic layer was separated and the aqueous solution further extracted with dichloromethane (2×20 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and the filtrate concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, 9:1 to 1:1 hexanes/ethyl acetate) to give ethyl 9-bromo-7-chloro-4,5-dihydro-3H-benzofuro[2,3-d]azepine-3-carboxylate (50 mg, 9%) as an off-white solid: 1H NMR (CDCl3, 300 MHz) δ 7.56 (d, J=1.7 Hz, 1H), 7.39 (d, J=1.6 Hz, 1H), 7.08-6.82 (m, 1H), 5.88-5.70 (m, 1H), 4.38 (q, J=7.1 Hz, 2H), 3.90 (t, J=5.1 Hz, 2H), 3.26 (t, J=5.0 Hz, 2H), 1.34 (t, J=7.0 Hz, 3H).

Workup

  1. custombefore being quenched by addition of aqueous sodium bicarbonate solution
  2. customThe organic layer was separated
  3. extractionthe aqueous solution further extracted with dichloromethane (2×20 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated in vacuo
  7. customThe residue was purified by flash column chromatography (SiO2, 9:1 to 1:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-d9c431a09b694f238f7ffc7a01d62d84
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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