Trifluoroacetic acid → ethyl 9-bromo-7-chloro-4,5-dihydro-1H-benzofuro[2,3-d]azepine-3(2H)-carboxylate

HRID 2179430Notes

Reaction equation

HRID 2179430 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([Cl:21])[C:5]2[O:20][C:9]3[CH2:10][CH2:11][N:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:13]=[CH:14][C:8]=3[C:6]=2[CH:7]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>>[Br:1][C:2]1[CH:3]=[C:4]([Cl:21])[C:5]2[O:20][C:9]3[CH2:10][CH2:11][N:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:13][CH2:14][C:8]=3[C:6]=2[CH:7]=1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 68109610ethyl 9-bromo-7-chloro-4,5-dihydro-3H-benzofuro[2,3-d]azepine-3-carboxylate

Product 1

HCID 68109096ethyl 9-bromo-7-chloro-4,5-dihydro-1H-benzofuro[2,3-d]azepine-3(2H)-carboxylateYield 99.1%

Procedure

To a solution of the product of step C (50 mg, 0.13 mmol) and trifluoroacetic acid (0.75 mL) at 0° C. was added triethylsilane (64 μL, 0.40 mmol). The reaction was allowed to warm to ambient temperature over 14 h then quenched by addition of aqueous sodium bicarbonate solution. The mixture was extracted with dichloromethane (2×20 mL) and the combined organic extracts 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-1H-benzofuro[2,3-d]azepine-3(2H)-carboxylate (48 mg, 96%) as a colorless oil: 1H NMR (CDCl3, 300 MHz) δ 7.45-7.38 (m, 1H), 7.35 (d, J=1.4 Hz, 1H), 4.20 (q, J=7.1 Hz, 2H), 3.78-3.67 (m, 4H), 3.20-3.10 (m, 2H), 2.88-2.75 (m, 2H), 1.29 (t, J=7.0 Hz, 3H).

Workup

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

Sources & evidence

ORD record
ord-105c1b9741f548d78652c923698b9661
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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