Ethylene Glycol → 10-[2-(Trifluoromethoxy)phenyl]-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole

HRID 2307039Notes

Reaction equation

HRID 2307039 reaction equation
C([N:9]1[CH2:22][CH2:21][C:20]2[C:19]3[C:18]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[O:29][C:30]([F:33])([F:32])[F:31])=[CH:17][CH:16]=[CH:15][C:14]=3[NH:13][C:12]=2[CH2:11][CH2:10]1)(=O)C1C=CC=CC=1.C(O)CO.[OH-].[K+].CCOC(C)=O>O>[F:33][C:30]([F:31])([F:32])[O:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[C:18]1[C:19]2[C:20]3[CH2:21][CH2:22][NH:9][CH2:10][CH2:11][C:12]=3[NH:13][C:14]=2[CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 8857Ethyl AcetateHCID 14797Potassium HydroxideHCID 223965673-Benzoyl-10-[2-(trifluoromethoxy)phenyl]-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole

Product 1

HCID 2239658210-[2-(Trifluoromethoxy)phenyl]-1,2,3,4,5,6-hexahydroazepino[4,5-b]indoleYield 69%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
170 °C

Procedure

3-Benzoyl-10-[2-(trifluoromethoxy)phenyl]-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (1.55 g, 3.44 mmol) and ethylene glycol (50 mL) were combined and heated to 170° C. KOH (3.91 g, 69.7 mmol) was added and the reaction mixture was stirred at 170° C. for 1.5 h. The reaction mixture was cooled to rt and was combined with EtOAc (100 mL) and H2O (300 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 to give crude product (5.22 g). The crude product was chromatographed (SiO2 100 g, eluted with 90:10:1 CH2Cl2:CH3OH:conc. NH4OH) to give 10-[2-(trifluoromethoxy)phenyl]-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (0.82 g) in 69% yield. 1H NMR (400 MHz, CD3OD) δ 2.24-2.36, 2.70-2.76, 2.95-3.03, 6.75, 7.06, 7.30, 7.36-7.42, 7.46-7.51; MS (ESI+) for C19H17F3N2O m/z 347.2 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give crude product (5.22 g)
  8. customThe crude product was chromatographed
  9. wash(SiO2 100 g, eluted with 90:10:1 CH2Cl2:CH3OH:conc. NH4OH)

Sources & evidence

ORD record
ord-20fd7bfe47a14d168bead4d43cfcfb7d
Source dataset
uspto-grants-2004_12
Patent number
US06828314B2

Reaction notes

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