Sodium Carbonate → 3-Benzoyl-10-[2-(trifluoromethoxy)phenyl]-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole

HRID 1356355Notes

Reaction equation

HRID 1356355 reaction equation
[C:1]([N:9]1[CH2:22][CH2:21][C:20]2[C:19]3[C:18](Br)=[CH:17][CH:16]=[CH:15][C:14]=3[NH:13][C:12]=2[CH2:11][CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:24][C:25]([F:37])([F:36])[O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([N:9]1[CH2:22][CH2:21][C:20]2[C:19]3[C:18]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=4[O:26][C:25]([F:24])([F:37])[F:36])=[CH:17][CH:16]=[CH:15][C:14]=3[NH:13][C:12]=2[CH2:11][CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27772042-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 223966193-Benzoyl-10-bromo-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole

Product 1

HCID 223965673-Benzoyl-10-[2-(trifluoromethoxy)phenyl]-1,2,3,4,5,6-hexahydroazepino[4,5-b]indoleYield 29.4%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 241BenzeneSolvent

Procedure

3-Benzoyl-10-bromo-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (4.00 g, 10.8 mmol) was suspended in benzene (170 mL). 2-(Trifluoromethoxy)-phenylboronic acid (4.48 g, 21.7 mmol), trans-dichlorobis(triphenylphosphine)palladium(II) (0.433 g, 0.617 mmol) and 2M Na2CO3 (17.6 mL) were added to the reaction mixture. Ar was bubbled through the reaction mixture for 20 min. The reaction mixture was heated at reflux for 11 h. After cooling, the reaction mixture was concentrated. The residue was combined with EtOAc (250 mL) and H2O (400 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were dried over MgSO4, filtered and concentrated. The crude product (7.95 g) was recrystallized from CH3OH to yield 3-benzoyl-10-[2-(trifluoromethoxy)phenyl]-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (1.43 g). The crude product from the mother liquors was chromatographed (SiO2 250 g, eluted with 2:1 toluene:EtOAc) to give 3-benzoyl-10-[2-(trifluoromethoxy)phenyl]-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (5.21 g). The yield of the reaction was 87%. IR (diffuse reflectance) 3266, 3227, 3187, 1615, 1574, 1498, 1483, 1464, 1428, 1382, 1354, 1334, 1323, 1288, 1253, 1221, 1202, 1167, 926, 790, 767, 750, 732, 704, 626 cm−1; MS (ESI+) for C26H21F3N2O2 m/z 450.9 (M+H)+; Anal. Calcd for C26H21F3N2O2: 4.70; N, 6.22; found: C, 69.25; H, 4.78; N, 6.25.

Workup

  1. customAr was bubbled through the reaction mixture for 20 min
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux for 11 h
  4. temperatureAfter cooling
  5. concentrationthe reaction mixture was concentrated
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product (7.95 g) was recrystallized from CH3OH

Sources & evidence

ORD record
ord-86a9596f71d8483c83e4144cc67eda7a
Source dataset
uspto-grants-2003_07
Patent number
US06586421B2

Reaction notes

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