Chloro-N,N-diethylacetamide → 4-Amino-5-chloro-2-[2-(diethylamino)-2-oxoethoxy]benzoic acid methyl ester

HRID 846604Notes

Reaction equation

HRID 846604 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:15])[C:6]1[CH:11]=[C:10]([Cl:12])[C:9]([NH2:13])=[CH:8][C:7]=1[OH:14].Cl[CH2:17][C:18]([N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[O:19]>CN(C)C=O>[CH3:3][O:4][C:5](=[O:15])[C:6]1[CH:11]=[C:10]([Cl:12])[C:9]([NH2:13])=[CH:8][C:7]=1[O:14][CH2:17][C:18]([N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[O:19]

Participants

5

Reactant 3

HCID 16844Chloro-N,N-diethylacetamideHCID 24758Sodium hydrideHCID 14883223Methyl 4-amino-5-chloro-2-hydroxybenzoate2×

Product 1

HCID 537123184-Amino-5-chloro-2-[2-(diethylamino)-2-oxoethoxy]benzoic acid methyl esterYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A cooled (0° C.) suspension of 60% sodium hydride/oil dispersion (1.40 g, 0.035 mole) in anhydrous dimethylformamide (60 ml) under nitrogen was treated in portions with 4-amino-5-chloro-2-hydroxybenzoic acid methyl ester (6.05 g, 0.030 mole) and stirred for 30 minutes at room temperature. 2-Chloro-N,N-diethylacetamide (5.40 g, 0.036 mole) was added, and the mixture was stirred at 100°-110° C. for 3 hours until gas chromatography indicated absence of 4-amino-5-chloro-2-hydroxybenzoic acid methyl ester. The solution was cooled and added to ice water (350 ml), then extracted with ether (3×200 ml). The combined organic solution was dried (magnesium sulfate) and concentrated in vacuo. Filtration through alumina (eluted with 3% methanol/methylene chloride) and trituration from petroleum ethers (30°-60°) afforded 8.66 g (92%) of 4-amino-5-chloro-2-[2-(diethylamino)-2-oxoethoxy]benzoic acid methyl ester as a colorless solid; mp 97.5° -99.5° C. (ethyl acetate/hexane).

Workup

  1. temperatureA cooled
  2. stirringthe mixture was stirred at 100°-110° C. for 3 hours until gas chromatography
  3. temperatureThe solution was cooled
  4. extractionextracted with ether (3×200 ml)
  5. dry with materialThe combined organic solution was dried (magnesium sulfate)
  6. concentrationconcentrated in vacuo
  7. filtrationFiltration through alumina (eluted with 3% methanol/methylene chloride) and trituration from petroleum ethers (30°-60°)

Sources & evidence

ORD record
ord-a9d165a4f552427d8e71b450b62273c7
Source dataset
uspto-grants-1992_08
Patent number
US05137895

Reaction notes

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