Sodium hydride → 4-(1-Benzyl-3-carbamoylmethyl-2-methyl-1H-indol-6-yloxy)-butyric acid ethyl ester

HRID 1069582Notes

Reaction equation

HRID 1069582 reaction equation
[OH:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:19][C:20]([NH2:22])=[O:21])=[C:7]([CH3:18])[N:8]2[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:26][CH2:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30].C(Cl)Cl.CO.CCCCCC>O>[CH2:32]([O:31][C:29](=[O:30])[CH2:28][CH2:27][CH2:26][O:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:19][C:20]([NH2:22])=[O:21])=[C:7]([CH3:18])[N:8]2[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:4][CH:3]=1)[CH3:33]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 76300Ethyl 4-bromobutyrateHCID 105657326-hydroxy-2-methyl-1-(phenylmethyl)-1H-indole-3-acetamideHCID 21959077Hexane methylene chloride methanol

Product 1

HCID 105735094-(1-Benzyl-3-carbamoylmethyl-2-methyl-1H-indol-6-yloxy)-butyric acid ethyl esterYield 76%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 294 mg (1 mmol) of 6-hydroxy-2-methyl-1-(phenylmethyl)-1H-indole-3-acetamide was treated with 40 mg (1 mmol) of 60% NaH/mineral oil and after 1 hours, 0.15 mL (1 mmol) of ethyl 4-bromobutyrate was added. The mixture was stirred for 2 hours, diluted with water and extracted with EtOAc. The EtOAc solution was washed with NaCl solution, dried (MgSO4), and concentrated at reduced pressure. The residue was chromatographed on silica eluting with EtOAc to give (after crystallizing from CH2Cl2/MeOH/hexane, 228 mg (76% yield) of 4-[[3-(2-amino-2-oxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-6-yl]oxy]butanoic acid ethyl ester, mp, 126-133° C.

Workup

  1. extractionextracted with EtOAc
  2. washThe EtOAc solution was washed with NaCl solution
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated at reduced pressure
  5. customThe residue was chromatographed on silica eluting with EtOAc
  6. customto give (

Sources & evidence

ORD record
ord-b0822de911be4d3e926d6fc04d5bdc5f
Source dataset
uspto-grants-2001_06
Patent number
US06252084B1

Reaction notes

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