Triethylamine → N1-(2,2-dimethoxyethyl)-N2-(4-(2-hydroxy-2-methylpropoxy)-3-methylphenyl)oxalamide

HRID 906239Notes

Reaction equation

HRID 906239 reaction equation
Cl[C:2](=[O:8])[C:3](OCC)=[O:4].[NH2:9][C:10]1[CH:21]=[CH:20][C:13]([O:14][CH2:15][C:16]([CH3:19])([OH:18])[CH3:17])=[C:12]([CH3:22])[CH:11]=1.CCN(CC)CC.[CH3:30][O:31][CH:32]([O:35][CH3:36])[CH2:33][NH2:34]>C1COCC1.CCOC(C)=O>[CH3:30][O:31][CH:32]([O:35][CH3:36])[CH2:33][NH:34][C:2](=[O:8])[C:3]([NH:9][C:10]1[CH:21]=[CH:20][C:13]([O:14][CH2:15][C:16]([OH:18])([CH3:19])[CH3:17])=[C:12]([CH3:22])[CH:11]=1)=[O:4]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 20884Ethoxalyl chlorideHCID 89728Aminoacetaldehyde dimethyl acetalHCID 575405781-(4-Amino-2-methylphenoxy)-2-methylpropan-2-ol

Product 1

HCID 57540557N1-(2,2-dimethoxyethyl)-N2-(4-(2-hydroxy-2-methylpropoxy)-3-methylphenyl)oxalamideYield 98.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Slow addition of a solution of ethyl 2-chloro-2-oxoacetate (4.69 g, 34.4 mmol) in THF (30 ml) to a solution of 1-(4-amino-2-methylphenoxy)-2-methylpropan-2-ol (6.10 g, 31.2 mmol) in THF (100 mL) resulted in formation of a precipitate as the reaction stirred at RT for 30 min. At which time a solution of Et3N (13.06 mL, 94 mmol) and 2,2-dimethoxyethanamine (3.94 g, 37.5 mmol) in EtOAc (100 mL) was added prior to heating the mixture at reflux for 25 hours. After cooling and concentration under vacuum, the residue, following dilution with CH2Cl2, was extracted with aqueous 0.5 N HCl (2×150 ml). The CH2Cl2 layer was dried over sodium sulfate and concentrated to yield N1-(2,2-dimethoxyethyl)-N2-(4-(2-hydroxy-2-methylpropoxy)-3-methylphenyl)-oxalamide (11.40 g, 30.6 mmol, 98% yield) as white solid which was carried forward without further purification.

Workup

  1. customresulted in formation of a precipitate as the reaction
  2. temperatureto heating the mixture
  3. temperatureat reflux for 25 hours
  4. temperatureAfter cooling
  5. concentrationconcentration under vacuum
  6. extractionwas extracted with aqueous 0.5 N HCl (2×150 ml)
  7. dry with materialThe CH2Cl2 layer was dried over sodium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-db3170a291f94157851b6a3d7b348187
Source dataset
uspto-grants-2011_09
Patent number
US08012984B2

Reaction notes

Loading…