Indole → 5-(2,2,2-trifluoroethoxy)-1H-indole-3-carboxylic acid

HRID 57315

Reaction equation

HRID 57315 reaction equation
CC1C=[C:4]([OH:11])C=CC=1[N+]([O-])=O.[H-].[Na+].C1([O-:20])C=CC=CC=1.S(C1C=CC(C)=CC=1)(OCC(F)(F)F)(=O)=O.F[C:38](F)(F)[CH2:39][O:40][CH2:41][C:42]([F:45])([F:44])[F:43].[NH:48]1[C:56]2[C:51](=[CH:52]C=C[CH:55]=2)[CH:50]=[CH:49]1>CN(P(N(C)C)(N(C)C)=O)C>[F:43][C:42]([F:45])([F:44])[CH2:41][O:40][C:39]1[CH:52]=[C:51]2[C:56](=[CH:55][CH:38]=1)[NH:48][CH:49]=[C:50]2[C:4]([OH:11])=[O:20]

Participants

8

Reactant 6

HCID 798IndoleHCID 9528FlurothylHCID 174123-Methyl-4-nitrophenolHCID 24758Sodium hydrideHCID 67942Ethanol, 2,2,2-trifluoro-, 1-(4-methylbenzenesulfonate)HCID 119047Phenolate

Product 1

HCID 576465175-(2,2,2-trifluoroethoxy)-1H-indole-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 12679HexamethylphosphoramideSolvent

Procedure

5-(2,2,2-trifluoroethoxy)-1H-indole-3-carboxylic acid was prepared following the procedure reported in Synthesis (1980) 727. 3-methyl-4-nitrophenol (Aldrich) was deprotonated with sodium hydride in HMPA, and the resulting phenolate alkylated with 2,2,2-trifluoroethyl tosylate (Aldrich). The resulting trifluoroethyl ether was then converted to the indole using the Batcho-Leimgruber protocol. Formylation and oxidation as described herein gave the title compound as an off-white solid. MS (m/e) 260.

Workup

  1. custom5-(2,2,2-trifluoroethoxy)-1H-indole-3-carboxylic acid was prepared
  2. customreported in Synthesis (1980) 727

Sources & evidence

ORD record
ord-4d827cc537484e228c849fdeaddc49cf
Source dataset
uspto-grants-2016_09
Patent number
US09434724B2

Linked notes

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