FLUORINATED BETA-PHENYL-ALPHA-METHYLETHYLAMINES

• Main Authors: FULLER R,US, MOLLOY B,US, HAUSER K,US
• Format: Patent
• Language: English
• Published: 06.03.1973
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

1391305 #-Phenyl-#-fluoro-α-methylethylamines ELI LILLY & CO 13 July 1972 [14 July 1971] 32848/72 Heading C2C Novel # phenyl-#-fluoro-α-methylethylamines of the general formula wherein R is a hydrogen or halogen atom, R1 is a hydrogen or fluorine atom, B2 is a group and R3 is a hydrogen atom or methyl group, and non-toxic acid addition salts thereof are prepared (a) when R3 is a hydrogen atom, by acid hydrolysis of the corresponding amide of the above general formula wherein R2 is a -CH(CH 3 )NHCHO group and (b) by reduction of the corresponding azide of the above general formula wherein R2 is a -C(R3)(CH 3 )N 3 group with sodium borohydride, followed optionally by salification of the product. The amide starting materials are prepared by reaction of a carboxylic acid of the above general formula wherein R2 is COOH with methyl lithium in ether, followed by saturated NH 4 Cl solution, and reaction of the resulting ketone of the above general formula wherein R2 is -COCH 3 with formic acid and formamide. α,α-Difluorophenylacetic acid is prepared by reaction of phenylacetonitrile with sulphuryl chloride, reaction of the resulting α,α-dichlorophenylacetonitrile with antimony trifluoride, treatment of the resulting x,x-difiuorophenyl. acetonitrile with concentrated H 2 SO 4 and alkaline hydrolysis of the resulting α,α-difluorophenylacetamide. α,α-Difluoro-4-chlorophenylacetic acid is prepared analogously. The azide starting materials are prepared by treatment of the corresponding bromide of the above general formula wherein R2 is a group with sodium azide. 1 -Phenyt- 1 fiuero-2.bromopropane is prepared by reaction of #-methylstyrene with a pyridine -HF salt and N-bromoacetamide. 1,1-Difluoro- 1-phenyl-2-bromopropane is prepared by treatment of α-bromopropiophenone with sulphur tetrafluoride and 1,1-difluoro-1-phenyl-2-bromo- 2-methylpropane is prepared in the same way. Pharmaceutical compositions having sympathetic nervous system stimulating activity comprise, as active ingredient, a #-phenyl-#- fluoro-α-methylethylamine of the above general formula, together with a pharmaceutically acceptable carrier.