Triethyl phosphonoacetate → Ethyl 4-(2,2,3,3-tetrafluoropropoxy)cinnamate
Reaction equation
[F:1][C:2]([F:16])([CH:13]([F:15])[F:14])[CH2:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1.[CH2:17]([O:19][C:20]([CH2:22]P(OCC)(=O)OCC)=[O:21])[CH3:18]>>[F:1][C:2]([F:16])([CH:13]([F:15])[F:14])[CH2:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=[CH:22][C:20]([O:19][CH2:17][CH3:18])=[O:21])=[CH:7][CH:6]=1Participants
Procedure
Prior-art syntheses of 4-fluoroalkoxycinnamonitriles start, for example, from p-chlorobenzonitrile, which is reacted, in a first reaction step, with 2,2,3,3'tetra-fluoropropanol to give 4-(2,2,3,3-tetrafluoropropoxy)benzonitrile (EP 0 472 392). This reaction has already been described by J. P. Idoux (J. Org. Chem. 48, 3772, 1983). In a second reaction step, 4-(2,2,3,3-tetrafluoropropoxy)benzonitrile is reacted in the presence of metal hydrides, such as diisobutylaluminumhydride, to give the corresponding benzaldehyde (JPS Sho 61-72767). 4-(2,2,3,3-tetrafluoropropoxy)-benzaldehyde subsequently reacts with diethyl ethoxycarbonylmethanephosphonate to give ethyl 4-(2,2,3,3-tetrafluoropropoxy)cinnamate, which is hydrolyzed, in a fourth step, to give free cinnamic acid. The fifth reaction step consists in the formation of the cinnamoyl chloride, which, in a sixth reaction step, reacts with aqueous ammonia to give 4-(2,2,3,3-tetrafluoropropoxy) cinnamamide. In the seventh and last step of the reaction sequence, the abovementioned cinnamamide is reacted in the presence of thionyl chloride or phosphorus pentachloride to give the desired product.
Sources & evidence
- ORD record
- ord-384d8ee609934254940141ddaf85b12e
- Source dataset
- uspto-grants-1996_10
- Patent number
- US05569776
Reaction notes
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