Water → 1-[2-(tert-Butoxycarbonyl-methyl-amino)-ethyl]-6-chloro-1H-indole-3-carboxylic acid

HRID 1097837Notes

Reaction equation

HRID 1097837 reaction equation
[C:1]([O:5][C:6](=[O:27])[N:7]([CH2:9][CH2:10][N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([Cl:20])[CH:18]=2)[C:13]([C:21](=[O:26])C(F)(F)F)=[CH:12]1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[OH2:30]>CN(C)C=O>[C:1]([O:5][C:6]([N:7]([CH3:8])[CH2:9][CH2:10][N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([Cl:20])[CH:18]=2)[C:13]([C:21]([OH:26])=[O:30])=[CH:12]1)=[O:27])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 962Water2×HCID 24758Sodium hydrideHCID 66811026{2-[6-Chloro-3-(2,2,2-trifluoro-acetyl)-indol-1-yl]-ethyl}-methyl-carbamic acid tert-butyl ester

Product 1

HCID 597567001-[2-(tert-Butoxycarbonyl-methyl-amino)-ethyl]-6-chloro-1H-indole-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 15.4 g (38.0 mmol) crude {2-[6-chloro-3-(2,2,2-trifluoro-acetyl)-indol-1-yl]-ethyl}-methyl-carbamic acid tert-butyl ester in 380 ml N,N-dimethylformamide were slowly added 11.0 g (228 mmol) sodium hydride (50%, dispersion in oil) followed by 3.40 ml (190 mmol) water at 15-22° C. After stirring for 1 h at room temperature 500 ml water were added slowly. The mixture was washed with two 300-ml portions of tert-butyl methyl ether. The combined organic layers were extracted with 300 ml of a 0.5 M aqueous solution of sodium hydroxide. The combined aqueous layers were acidified to pH 2 with an ice-cold 4 M aqueous solution of hydrochloric acid at 0-5° C. and extracted with two 400-ml portions of ethyl acetate.

Workup

  1. additionwere added slowly
  2. washThe mixture was washed with two 300-ml portions of tert-butyl methyl ether
  3. extractionThe combined organic layers were extracted with 300 ml of a 0.5 M aqueous solution of sodium hydroxide
  4. customwere acidified to pH 2 with an ice-cold 4 M aqueous solution of hydrochloric acid at 0-5° C.
  5. extractionextracted with two 400-ml portions of ethyl acetate

Sources & evidence

ORD record
ord-86d40ee18f7146bda3842afe01d88910
Source dataset
uspto-grants-2012_03
Patent number
US08143281B2

Reaction notes

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