HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

Sodium hydride → N-[2-(3,4-Dimethoxyphenyl)ethyl]-alpha-{2-chloro-4-[2-(ethoxycarbonylamino)propionyl]phenoxy}acetamide

HRID 1198901
Notes
Print preview

Reaction equation

HRID 1198901 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9](=[O:18])[CH:10]([NH:12][C:13](=[O:17])[O:14][CH2:15][CH3:16])[CH3:11])[CH:5]=[CH:6][C:7]=1[OH:8].[H-].[Na+].Cl[CH2:22][C:23]([NH:25][CH2:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([O:36][CH3:37])[CH:29]=1)=[O:24]>CN(C)C=O>[CH3:37][O:36][C:30]1[CH:29]=[C:28]([CH2:27][CH2:26][NH:25][C:23](=[O:24])[CH2:22][O:8][C:7]2[CH:6]=[CH:5][C:4]([C:9](=[O:18])[CH:10]([NH:12][C:13]([O:14][CH2:15][CH3:16])=[O:17])[CH3:11])=[CH:3][C:2]=2[Cl:1])[CH:33]=[CH:32][C:31]=1[O:34][CH3:35]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 266222-Chloro-N-(2-(3,4-dimethoxy-phenyl)-ethyl)-acetamideHCID 14370691Ethyl N-[2-(3-chloro-4-hydroxyphenyl)-1-methyl-2-oxoethyl]carbamate

Product 1

HCID 14370692N-[2-(3,4-Dimethoxyphenyl)ethyl]-alpha-{2-chloro-4-[2-(ethoxycarbonylamino)propionyl]phenoxy}acetamideYield 61.1%

Reagents, catalysts & solvents 1

HCID 6228
Dimethylformamide
Solvent
2×

Procedure

505 mg of ethyl N-[2-(3-chloro-4-hydroxyphenyl)-1-methyl-2-oxoethyl]carbamate [prepared as described in step (b) above] were added to a suspension of 81 mg of sodium hydride (as a 55% w/w suspension in mineral oil) in 6 ml of anhydrous dimethylformamide, whilst ice-cooling. The mixture was then stirred at room temperature for 1 hour. The suspension was then cooled, and 476 mg of α-chloro-N-[2-(3,4-dimethoxyphenyl)ethyl]acetamide (prepared as described in Preparation 1) were added thereto. The mixture was stirred at room temperature for 2 hours and then at 100° C. (bath temperature) for 3 hours. At the end of this time, the dimethylformamide used as the solvent was removed by evaporation under reduced pressure, and water was added to the residue. The aqueous mixture was extracted with ethyl acetate, and the extract was washed with a saturated aqueous solution of sodium chloride, dried and concentrated by evaporation under reduced pressure. The residue was purified by column chromatography through silica gel. After elution of impurities with a 2:1 by volume mixture of ethyl acetate and hexane, 556 mg of the title compound were obtained from the fractions eluted with ethyl acetate as a pale yellow powder melting at 113°-114° C.

Workup

  1. temperaturewhilst ice-cooling
  2. temperatureThe suspension was then cooled
  3. stirringThe mixture was stirred at room temperature for 2 hours
  4. waitat 100° C. (bath temperature) for 3 hours
  5. customwas removed by evaporation under reduced pressure, and water
  6. additionwas added to the residue
  7. extractionThe aqueous mixture was extracted with ethyl acetate
  8. washthe extract was washed with a saturated aqueous solution of sodium chloride
  9. customdried
  10. concentrationconcentrated by evaporation under reduced pressure
  11. customThe residue was purified by column chromatography through silica gel
  12. washAfter elution of impurities with a 2:1
  13. additionby volume mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-28bcb1bd20994d8db8f08c3b5dbd359c
Source dataset
uspto-grants-1990_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US04898862

Reaction notes

Loading…

On this pageParticipantsProcedureWorkupSources & evidenceReaction notes