Formaldehyde → Chloromethyl 5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoate
Reaction equation
[NH2:1][S:2]([C:5]1[C:6]([Cl:21])=[CH:7][C:8]([NH:14][CH2:15][C:16]2[O:17][CH:18]=[CH:19][CH:20]=2)=[C:9]([CH:13]=1)[C:10](Cl)=[O:11])(=[O:4])=[O:3].C=[O:23].Cl[CH2:25][Cl:26]>>[NH2:1][S:2]([C:5]1[C:6]([Cl:21])=[CH:7][C:8]([NH:14][CH2:15][C:16]2[O:17][CH:18]=[CH:19][CH:20]=2)=[C:9]([CH:13]=1)[C:10]([O:23][CH2:25][Cl:26])=[O:11])(=[O:4])=[O:3]Participants
Conditions
- Temperature
- 90 °C
Procedure
A mixture of 5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyl chloride (13) (0.040 mole) and paraformaldehyde (0.040 mole) is heated in a sealed vessel at 90° C. for 3 hours. The reaction is cooled, and the solids dissolved in dichloromethane. The solution is washed with 5% aqueous sodium bicarbonate, with water, and then with a saturated sodium chloride solution. The organic layer is dried over sodium sulfate, filtered and concentrated in vacuo to give crude product, which may be purified by column chromatography on silica gel with hexanes/ethyl acetate as eluent. The fractions that contain pure product may be combined and spin evaporated in vacuo to give chloromethyl 5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoate (15). See eg., Bodor, et al., J. Med. Chem., 23, 469 (1980), and Ulich, et al., J. Am. Chem. Soc., (1921) 43: 660.
Workup
- temperatureThe reaction is cooled
- washThe solution is washed with 5% aqueous sodium bicarbonate, with water
- dry with materialThe organic layer is dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customto give crude product, which
- custommay be purified by column chromatography on silica gel with hexanes/ethyl acetate as eluent
- customspin evaporated in vacuo
Sources & evidence
- ORD record
- ord-4b96aa9a517449fc9a17a54d1f132b9d
- Source dataset
- uspto-grants-2010_07
- Patent number
- US07763612B2
Reaction notes
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