Chloride → 5-(Chloromethyl)-2,2-difluorobenzo[d][1,3]dioxole
Reaction equation
[Cl-:1].S(Cl)(Cl)=O.[F:6][C:7]1([F:19])[O:11][C:10]2[CH:12]=[CH:13][C:14]([C:16](O)=O)=[CH:15][C:9]=2[O:8]1>>[Cl:1][CH2:16][C:14]1[CH:13]=[CH:12][C:10]2[O:11][C:7]([F:19])([F:6])[O:8][C:9]=2[CH:15]=1Participants
Procedure
The starting material, 2,2-difluorobenzo[d][1,3]dioxole-5-carboxylic acid, is commercially available from Saltigo (an affiliate of the Lanxess Corporation). Reduction of the carboxyls acid moiety in 2,2-difluorobenzo[d][1,3]dioxole-5-carboxylic acid to the primary alcohol, followed by conversion to the corresponding chloride using thionyl chloride (SOCl2), provides 5-(chloromethyl)-2,2-difluorobenzo[d][1,3]dioxole, which is subsequently converted to 2-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)acetonitrile using sodium cyanide. Treatment of 2-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)acetonitrile with base and 1-bromo-2-chloroethane provides 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarbonitrile. The nitrile moiety in 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarbonitrile is converted to a carboxylic acid using base to give 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxylic acid, which is converted to the desired acid chloride using thionyl chloride.
Sources & evidence
- ORD record
- ord-e235dac172b64f3dbafba47f9af95a30
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08552034B2
Reaction notes
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