Chloro-N,N-diethylacetamide → HCID 20066025, compound

HRID 359063Notes

Reaction equation

HRID 359063 reaction equation
[CH2:1]([N:8]([CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1)[CH2:9][CH:10]([OH:19])[CH2:11][O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].[CH2:35]([N:37]([CH2:42][CH3:43])[C:38](=[O:41])[CH2:39]Cl)[CH3:36]>C(COC)OC.CCOCC>[CH2:35]([N:37]([CH2:42][CH3:43])[C:38](=[O:41])[CH2:39][O:28][C:25]1[CH:24]=[CH:23][C:22]([CH2:21][CH2:20][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:9][CH:10]([OH:19])[CH2:11][O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:27][CH:26]=1)[CH3:36]

Participants

6

Reactant 3

HCID 16844Chloro-N,N-diethylacetamideHCID 15034359HCID 15034359, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 20066025HCID 20066025, compoundYield 99.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

4-[2-(N-Benzyl-N-(2-hydroxy-3-phenoxypropyl)amino)ethyl]phenol (5.1 g) was added to a stirred solution of potassium t-butoxide (1.57 g) in dimethoxyethane (100 ml). To the resulting solution was added N,N-diethylchloroacetamide (2.1 g) and the mixture was stirred for two hours. The mixture was diluted with ether (300 ml) and washed with brine (2×20 ml). The solution was dried (MgSO4) and evaporated under reduced pressure to yield the crude intermediate (12.5 g). The crude intermediate was purified by chromatography on K60 silica (225 g) using a gradient mixture of methanol and dichloromethane (1% to 3% of methanol) to give N,N-diethyl-4-[2-(N-benzyl-N-(2-hydroxy-3-phenoxypropyl)amino)ethyl]-phenoxyacetamide (6.6 g) as a gum. The gum was dissolved in methanol (400 ml) and treated with 10% palladium on carbon (380 mg). The mixture was stirred under an atmosphere of hydrogen for 4 hours. The catalyst was removed by filtration through Kieselguhr, and the filtrate evaporated to give the product (5.0 g) as a colourless oil, which was dissolved in dichloromethane (300 ml) and acidified to pH3with ethereal hydrogen chloride. The solvent was removed by evaporation and replaced with fresh dichloromethane which also was evaporated. The residual gum was dissolved in methyl acetate from which it crystallised as N,N-diethyl-4-[2-(2-hydroxy-3-phenoxypropylamino)ethyl]phenoxyacetamide hydrochloride (4.49 g) m.p. 113°-5° C.; NMR: 1.05[t,3H, CH3 ]; 1.15[t,3H, CH3 ]; 2.90-3.08[m,2H, CH2C6H4 ]; 3.08-3.45(m,8H, CH2NCH2 +CH2NHCH2 ]; 4.0[m,2H,PhOCH2 ]; 4.25[m,CHOH]; 4.75[s,2H,OCH2CO]; 6.85-7.05[m,5H, aromatic H]; 7.25-7.4[m,4H, aromatic H]: microanalysis: found: C, 62.9; H,7.6; N, 6.1; Cl 8.3%; C23H32N2O4.HCl requires: C, 63.2; H,7.6; N, 6.4; Cl 8.1%.

Workup

  1. washwashed with brine (2×20 ml)
  2. dry with materialThe solution was dried (MgSO4)
  3. customevaporated under reduced pressure
  4. customto yield the crude intermediate (12.5 g)
  5. customThe crude intermediate was purified by chromatography on K60 silica (225 g)
  6. additiona gradient mixture of methanol and dichloromethane (1% to 3% of methanol)

Sources & evidence

ORD record
ord-f78cb775f85b416f9b35341a11cf1aab
Source dataset
uspto-grants-1991_03
Patent number
US04999377

Reaction notes

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