Ethyl 3-chloro-3-oxopropionate → N-(4-methanesulfonylamino-2-sulfamoyl-phenyl)-malonamic acid ethyl ester

HRID 730545Notes

Reaction equation

HRID 730545 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])=[CH:4][C:3]=1[S:13]([NH2:16])(=[O:15])=[O:14].Cl[C:18](=[O:25])[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21]>CN(C)C(=O)C.C(OCC)C.C(OCC)(=O)C>[CH2:23]([O:22][C:20](=[O:21])[CH2:19][C:18]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([CH3:12])(=[O:10])=[O:11])=[CH:4][C:3]=1[S:13](=[O:14])(=[O:15])[NH2:16])=[O:25])[CH3:24]

Participants

6

Reactant 2

HCID 118931Ethyl 3-chloro-3-oxopropionateHCID 249506572-Amino-5-[(methylsulfonyl)amino]benzenesulfonamide

Product 1

HCID 24858398N-(4-methanesulfonylamino-2-sulfamoyl-phenyl)-malonamic acid ethyl esterYield 97.4%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
25 °C

Procedure

2-Amino-5-methanesulfonylamino-benzenesulfonamide (Example 17d, 23.27 g, 87.81 mmol) was dissolved in N,N-dimethylacetamide (100 mL) and diethyl ether (100 mL). Ethyl 3-chloro-3-oxo-propionate (13.88 g, 92.20 mmol) was added and the reaction mixture was stirred at 25° C. for 1 h. The reaction mixture was diluted with ethyl acetate (400 mL) and was extracted with water (400 mL). The aqueous layer was back-extracted with ethyl acetate (2×200 mL). The combined organic layers were dried over sodium sulfate, filtered and most of the solvent was removed in vacuo to a volume of ˜100 mL. To the stirred solution was added hexanes (100 mL) upon which a precipitate formed. The precipitate was collected by vacuum filtration, washed with hexanes and dried under high vacuum to afford the analytically pure product, N-(4-methanesulfonylamino-2-sulfamoyl-phenyl)-malonamic acid ethyl ester (31.22 g, 85.53 mmol, 97.4% yield) as a light-brown solid. 1H NMR (400 MHz, CD3OD) δ: 1.31 (3H, t, J=7.0 Hz), 3.00 (3H, s), 3.59 (2H, s), 4.25 (2H, quartet, J=6.9 Hz), 7.42-7.45 (1H, m), 7.86 (1H, m), 7.92 (1H, d, J=8.8 Hz).

Workup

  1. extractionwas extracted with water (400 mL)
  2. extractionThe aqueous layer was back-extracted with ethyl acetate (2×200 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered and most of the solvent
  5. customwas removed in vacuo to a volume of ˜100 mL
  6. additionTo the stirred solution was added hexanes (100 mL) upon which a precipitate
  7. customformed
  8. filtrationThe precipitate was collected by vacuum filtration
  9. washwashed with hexanes
  10. customdried under high vacuum

Sources & evidence

ORD record
ord-f032d7c7b67c42b0bac429c4b6ab89c4
Source dataset
uspto-grants-2009_09
Patent number
US07582754B2

Reaction notes

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