Ethoxalyl chloride → HCID 44902124, compound

HRID 906228Notes

Reaction equation

HRID 906228 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH2:10])=[CH:5][CH:4]=1.Cl[C:12](=[O:18])[C:13](OCC)=[O:14].[CH3:19][O:20][CH:21]([O:24][CH3:25])[CH2:22][NH2:23].C(N(CC)C(C)C)(C)C.C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O>[CH3:19][O:20][CH:21]([O:24][CH3:25])[CH2:22][NH:23][C:12](=[O:18])[C:13]([NH:10][CH2:9][C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)=[O:14]

Participants

8

Reactant 5

HCID 20884Ethoxalyl chlorideHCID 754524-MethoxybenzylamineHCID 81531DiisopropylethylamineHCID 89728Aminoacetaldehyde dimethyl acetalHCID 516892Sodium Bicarbonate

Product 1

HCID 44902124HCID 44902124, compoundYield 35.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (4-methoxyphenyl)methanamine (9.90 g, 72.2 mmol) in THF (40 mL) was slowly added ethyl 2-chloro-2-oxoacetate (10.84 g, 79 mmol). After stirring the reaction at RT for 15 min, a solution of 2,2-dimethoxyethanamine (9.10 g, 87 mmol) and N,N-diisopropylethylamine (37.8 mL, 217 mmol) in EtOAc (40.0 mL) was added. The reaction was heated at reflux for 18 hours; whereupon, after cooling to RT, saturated NaHCO3 (50 ml) was added and the mixture extracted with EtOAc (50 ml). The EtOAc layer was dried over Na2SO4 and concentrated. The crude product was purified by silica gel chromatography employing a solvent gradient (CH2Cl2 to 5% MeOH/CH2Cl2) to elute N1-(2,2-dimethoxyethyl)-N2-(4-methoxybenzyl)oxalamide (7.50 g, 25.3 mmol, 35.1% yield) as white solid. 1H NMR (400 MHz, chloroform-d) δ ppm 9.07 (1H, s), 7.69 (1H, t, J=5.65 Hz), 7.59 (1H, d, J=8.78 Hz), 6.74 (1H, d, J=8.78 Hz), 4.46 (1H, t, J=5.40 Hz), 3.79 (2H, s), 3.53 (2H, t), 3.44 (6H, s), 2.23 (6H, d, J=5.27 Hz), 1.37 (6H, s).

Workup

  1. customthe reaction at RT for 15 min
  2. temperatureThe reaction was heated
  3. temperatureat reflux for 18 hours
  4. extractionthe mixture extracted with EtOAc (50 ml)
  5. dry with materialThe EtOAc layer was dried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-e261fc2c47b240589a0d41d18630637d
Source dataset
uspto-grants-2011_09
Patent number
US08012984B2

Reaction notes

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