5-Isothiazolecarboxaldehyde → 4-(5-Isothiazolyl)-3-butenoic acid
Reaction equation
[S:1]1[C:5]([CH:6]=O)=[CH:4][CH:3]=[N:2]1.C1(P(C2C=CC=CC=2)(C2C=CC=CC=2)=[CH:15][CH2:16][C:17]([O-:19])=[O:18])C=CC=CC=1.[Li+]>>[S:1]1[C:5]([CH:6]=[CH:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:4][CH:3]=[N:2]1Participants
Procedure
Reaction of isothiazole-5-carboxaldehyde with lithium 3-(triphenylphosphoranylidene)propanoate under standard Wittig conditions provides 4-(5-isothiazolyl)-3-butenoic acid which is reduced and cyclized with aluminum chloride to provide 4-oxo-4,5,6,7-tetrahydrobenzisothiazole. The 4-oxo compound is reacted with methylenetriphenyl phosphorane under standard Wittig conditions and a methylene is inserted into the resulting 4-methylene compound via a Simmons Smith reaction to provide 6,7-dihydrospiro [benzisothiazol-4 (SH), 1'-cyclopropane]which is oxidized with hydrogen peroxide in acetic acid to give 6,7-dihydrospiro[-3-oxo-benzisothiazol-4(5H),1'-cyclopropane 1,1-dioxide (4-spirocyclopropyl tetrahydrosaccharin). This is chloromethylated according to the procedure of Preparation 1A to give 2-chloromethyl-4-spirocyclopropyl-4,5,6,7-tetrahydrosaccharin.
Sources & evidence
- ORD record
- ord-527c342e0aec41bdab3d7b34eb52a602
- Source dataset
- uspto-grants-1996_10
- Patent number
- US05563163
Reaction notes
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