Sodium Hydroxide → 1-butyl-N,N-dimethyl-4,4-bis(3-methyl-5-(trifluoromethyl)-1H-indol-2-yl)cyclohexanamine

HRID 1011621Notes

Reaction equation

HRID 1011621 reaction equation
[CH2:1]([C:5]1([N:12]([CH3:14])[CH3:13])[CH2:10][CH2:9][C:8](=O)[CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4].[CH3:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:25]([F:28])([F:27])[F:26])[CH:23]=2)[NH:18][CH:17]=1.[F:29][C:30]([F:36])([F:35])S(O)(=O)=O.[OH-].[Na+]>ClCCl>[CH2:1]([C:5]1([N:12]([CH3:14])[CH3:13])[CH2:10][CH2:9][C:8]([C:17]2[NH:18][C:19]3[C:24]([C:16]=2[CH3:15])=[CH:23][C:22]([C:30]([F:36])([F:35])[F:29])=[CH:21][CH:20]=3)([C:17]2[NH:18][C:19]3[C:24]([C:16]=2[CH3:15])=[CH:23][C:22]([C:25]([F:28])([F:26])[F:27])=[CH:21][CH:20]=3)[CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 62406Trifluoromethanesulfonic acidHCID 44549958HCID 44549958, compoundHCID 57475098HCID 57475098, compound

Product 1

HCID 445175681-butyl-N,N-dimethyl-4,4-bis(3-methyl-5-(trifluoromethyl)-1H-indol-2-yl)cyclohexanamineYield 128.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-butyl-4-(dimethylamino)cyclohexanone (395 mg, 2 mmol, synthesis cf. WO2008009415, ketone unit Ket-4) together with 3-methyl-5-trifluoromethyl-1H-indole (398 mg, 2 mmol, synthesis cf. WO2008009415, indole unit Ind-7) was dissolved in dichloromethane (20 ml). Trifluoromethane sulphonic acid (0.2 ml, 338 mg, 2.25 mmol) was then added. This was stirred for 3 d at RT. For work up the reaction mixture was mixed with 1N NaOH (10 ml) and stirred for 10 min. After phase separation the aqueous phase was extracted with dichloromethane (2×10 ml). The combined organic phases were dried with sodium sulphate, filtered and concentrated to low volume in a vacuum. 741 mg of light brown solid was obtained, which was separated by chromatography [silica gel 60 (80 g); ethyl acetate/methanol (15:1; 1.51); (10:1; 500 ml); 1:1; 500 ml)].

Workup

  1. stirringstirred for 10 min
  2. customAfter phase separation the aqueous phase
  3. extractionwas extracted with dichloromethane (2×10 ml)
  4. dry with materialThe combined organic phases were dried with sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated to low volume in a vacuum

Sources & evidence

ORD record
ord-ffa0d863ef8d4dc181ba6320aa686260
Source dataset
uspto-grants-2011_07
Patent number
US07977370B2

Reaction notes

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