Hydrochloric Acid → Ethyl 6-chloro-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indole-5-carboxylate

HRID 339116

Reaction equation

HRID 339116 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([OH:13])=O)[NH:8]2)=[CH:4][C:3]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15].[F:19][C:20]([F:34])([F:33])[CH:21]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=1)[NH2:22].O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.Cl>CN(C)C=O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11](=[O:13])[NH:22][CH:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:30])([F:31])[F:32])[CH:24]=3)[C:20]([F:34])([F:33])[F:19])[NH:8]2)=[CH:4][C:3]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 231494114-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrateHCID 438251722,2,2-Trifluoro-1-(3-(trifluoromethyl)phenyl)ethanamineHCID 582479336-Chloro-5-(ethoxycarbonyl)-1H-indole-2-carboxylic acid

Product 1

HCID 58247983Ethyl 6-chloro-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indole-5-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of the crude 6-chloro-5-(ethoxycarbonyl)-1H-indole-2-carboxylic acid product (1.9 g) and 2,2,2-trifluoro-1-[3-trifluoromethylphenyl]ethanamine (1.12 g, 4.60 mmol) in N,N-dimethylformamide (15 ml) was admixed with 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (953 mg, 4.60 mmol) and stirred at room temperature for 4 days. The reaction solution was admixed with hydrochloric acid (1 M) and extracted with ethyl acetate. The organic phase was washed with sat. sodium hydrogencarbonate solution and saturated sodium chloride solution, dried over sodium sulphate, filtered and concentrated to dryness under reduced pressure. Column chromatography purification on silica gel with cyclohexane/ethyl acetate as the eluent (gradient from 10% ethyl acetate to 25% ethyl acetate).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic phase was washed with sat. sodium hydrogencarbonate solution and saturated sodium chloride solution
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure
  6. customColumn chromatography purification on silica gel with cyclohexane/ethyl acetate as the eluent (gradient from 10% ethyl acetate to 25% ethyl acetate)

Sources & evidence

ORD record
ord-8877e1ac52f44669b2877a89a943ee28
Source dataset
uspto-grants-2014_11
Patent number
US08889878B2

Linked notes

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