Sodium hydride → 5-[4-[[5-(2,5-Dimethylphenoxy)-2,2-dimethyl-1-oxopentyl]amino]phenoxy]-2,2-dimethylpentanoic acid, methyl ester

HRID 1639111Notes

Reaction equation

HRID 1639111 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:5]=1[O:6][CH2:7][CH2:8][CH2:9][C:10]([CH3:22])([CH3:21])[C:11]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1)=[O:12].Br[CH2:29][CH2:30][CH2:31][C:32]([CH3:38])([CH3:37])[C:33]([O:35][CH3:36])=[O:34]>CN(C)C=O>[CH3:3][C:4]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:5]=1[O:6][CH2:7][CH2:8][CH2:9][C:10]([CH3:22])([CH3:21])[C:11]([NH:13][C:14]1[CH:15]=[CH:16][C:17]([O:20][CH2:29][CH2:30][CH2:31][C:32]([CH3:38])([CH3:37])[C:33]([O:35][CH3:36])=[O:34])=[CH:18][CH:19]=1)=[O:12]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 13050502Methyl 5-bromo-2,2-dimethylpentanoateHCID 147495725-(2,5-dimethylphenoxy)-N-(4-hydroxyphenyl)-2,2-dimethylpentanamide

Product 1

HCID 147495735-[4-[[5-(2,5-Dimethylphenoxy)-2,2-dimethyl-1-oxopentyl]amino]phenoxy]-2,2-dimethylpentanoic acid, methyl esterYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride, 50% dispersion in mineral oil, 2.2 g, is added to 15.3 g of 5-(2,5-dimethylphenoxy)-N-(4-hydroxyphenyl)-2,2-dimethylpentanamide in 200 ml of N,N-dimethylformamide (DMF). Then 10 g of methyl 5-bromo-2,2-dimethylpentanoate (Journal of Medicinal Chemistry, Vol. 26, pp 1020-1027 (1983)) is added to the previous mixture. The mixture is stirred overnight and then stirred three hours on a steam bath, the DMF is removed on a rotary evaporator and water is added to the residue. The product is taken up in diethyl ether, extracted with base, washed with water and concentrated on a steam bath. Isopropyl ether is added to afford 10.4 g of 5-[4-[[5-(2,5-dimethylphenoxy)-2,2-dimethyl-1-oxopentyl]amino]-phenoxy]-2,2-dimethylpentanoic acid, methyl ester after recrystallization from isopropyl ether (2X); mp 62°-63° C.

Workup

  1. stirringstirred three hours on a steam bath
  2. customthe DMF is removed on a rotary evaporator and water
  3. additionis added to the residue
  4. extractionextracted with base
  5. washwashed with water
  6. concentrationconcentrated on a steam bath
  7. additionIsopropyl ether is added

Sources & evidence

ORD record
ord-fc9c4c241e9f4799984a4b75da83606f
Source dataset
uspto-grants-1989_11
Patent number
US04882357

Reaction notes

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