4-Hydroxymethylpyridine → Ethyl 5-trifluoromethyl-1-[(pyrid-4-yl)methyl]-1H-indole-2-carboxylate

HRID 1028037Notes

Reaction equation

HRID 1028037 reaction equation
N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[F:19][C:20]([F:36])([F:35])[C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][C:25]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:24]2.[N:37]1[CH:42]=[CH:41][C:40]([CH2:43]O)=[CH:39][CH:38]=1.C(P(CCCC)CCCC)CCC>C1(C)C=CC=CC=1>[F:36][C:20]([F:35])([F:19])[C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[N:26]([CH2:43][C:40]1[CH:41]=[CH:42][N:37]=[CH:38][CH:39]=1)[C:25]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:24]2

Participants

6

Reactant 4

HCID 114724-HydroxymethylpyridineHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 17389890Ethyl 5-(trifluoromethyl)-1H-indole-2-carboxylate

Product 1

HCID 68431838Ethyl 5-trifluoromethyl-1-[(pyrid-4-yl)methyl]-1H-indole-2-carboxylateYield 77.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A solution of 1.47 g (5.83 mmol) of 1,1′-(azodicarbonyl)dipiperidine in 50 ml of toluene is added dropwise to a solution of 1 g (3.89 mmol) of ethyl 5-trifluoromethyl-1H-indole-2-carboxylate, 0.63 g (5.83 mmol) of 4-pyridylcarbinol and 1.46 ml (5.83 mmol) of tributylphosphine in 50 ml of toluene. The reaction mixture is stirred overnight at room temperature and then concentrated under reduced pressure and chromatographed on a column of silica (eluent: dichloromethane/methanol). 1.05 g of expected product are obtained.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customchromatographed on a column of silica (eluent: dichloromethane/methanol)

Sources & evidence

ORD record
ord-eae5bccefdc641f8a8e086648680e252
Source dataset
uspto-grants-2014_05
Patent number
US08735432B2

Reaction notes

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