Methyl malonyl chloride → n-(4-Methanesulfonylamino-2-sulfamoylphenyl)malonamic acid methyl ester
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:24])[CH2:19][C:20]([O:22][CH3:23])=[O:21]>O1CCCC1>[CH3:23][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:24]Participants
Conditions
- Temperature
- 0 °C
Procedure
2-Amino-5-methanesulfonylamino-benzenesulfonamide (prepared as described in Example 1d, 1.70 kg, 6.40 mol) was dissolved in tetrahydrofuran (35 L), and was then cooled to 0° C. Methyl 3-chloro-3-oxopropionate (792 mL, 7.40 mol) was added slowly, and the resulting mixture was then allowed to warm to 23° C. and stirred for 2 days. The solvent was removed in vacuo, and the residue was then diluted with water (4 L) and saturated aqueous sodium bicarbonate solution (2 L). The resulting solid was filtered, and was then washed with water (5 L). The solid was suspended in hot methanol (15 mL/g), and was then cooled to 23° C. and filtered to afford the desired product, N-(4-methanesulfonylamino-2-sulfamoyl-phenyl)-malonamic acid methyl ester (1.68 kg, 4.61 mol, 72%), as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ: 3.02 (3H, s), 3.60 (2H, s), 3.66 (3H, s), 7.38 (1H, dd, J1=2.3 Hz, J2=8.6 Hz), 7.53 (2H, bs), 7.73 (1H, d, J=2.4 Hz), 7.83 (1H, d, J=8.7 Hz), 9.43 (1H, s), 9.99 (1H, s).
Workup
- temperatureto warm to 23° C.
- customThe solvent was removed in vacuo
- additionthe residue was then diluted with water (4 L) and saturated aqueous sodium bicarbonate solution (2 L)
- filtrationThe resulting solid was filtered
- washwas then washed with water (5 L)
- temperaturewas then cooled to 23° C.
- filtrationfiltered
Sources & evidence
- ORD record
- ord-9b07952a14fa4870b08cfd839d570c64
- Source dataset
- uspto-grants-2015_10
- Patent number
- US09156832B2
Reaction notes
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