The addition of N-lithiated amines to 1,1,1-trifluoromethylstyrene, a concise synthesis of 3- gem -difluoro-2-phenyl allylic amines

Synlett

Volumn 1995, Issue 6, 1995, Pages 659-660

  Bégué, Jean Pierre ^a   Bonnet Delpon, Danièle ^a   Rock, Michael H ^a  

^a UNIVERSITÉ PARIS SUD   (France)

Author keywords

1,1,1 trifluoromethylstyrene; 3 gem difluoro 2 phenyl allylic amines; N lithiated amines

Indexed keywords

EID: 0002921994     PISSN: 09365214     EISSN: 14372096     Source Type: Journal    
DOI: 10.1055/s-1995-5020     Document Type: Article

References (15)

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4. a)Synthesis of la has been reported by a sequence involving the addition of dibromodifluoromethane to the lithium anion of ethyl 2-(rerr-butoxycarbonyl)phenyl acetate followed by a 5 step conversion to the desired compound
5. McDonald, I.A.; Lacoste, J.M.; Bey, P; Palfreyman, M.G.; Zreika, M. J. Med. Chem. 1985, 28,186
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10. Typical procedure: I,l,l-Trifluoromethylstyrenel2 (0.52g, 0.003 mole) was added at-78C over 2 min to LDA prepared from nbutyllithium (1.36 ml,of a 2.5 M solution in hexanes) and diisopropylamine (0.56 ml, 0.0035 mole) in THF (20 ml). The pale yellow solution was stirred for one hour and allowed to warm to 0C over 1 hour. The brown solution was poured into saturated ammonium chloride solution, the layers separated and the aqueous phase extracted with diethylether (3 x 50 ml). The combined organics were dried and evaporated to afford a brown oil which was purified by passing through a short column of silica gel ( eluent pentane) to give the 3-gem-difluoro-2-phenyl allylic amines as a clear oil (0.68g, 90%). I.R neat micnrHvCC), 19F NMR (CDC13, CFCI3) 5-88.95 (d, J=42.4Hz)-92.5 (d, J=42.4Hz); 1/8NMR 5 0.95 (d, J=6.6Hz, 12H), 3.05 (sept J=6.6Hz, 2H) 3.45(dd, 2.8, 2.85Hz, 2H), 7.35 (M, 5H); 13C NMR 8 15.9, 38.0, 42.2, 87.5 (dd 1/8= 10.9, 10.95Hz) 122.6, 124.2, 124.5, 122.55, 129.15, 150.3 (d,d JCf=288.2, 288.5Hz) Anal. Calc, for C15H2iNF2: C 71.15, H 8.3, N 5.5 found; C 70.9, H, 8.0, N,5.1.
11. All new compounds were characterised by IR, 13/8 NMR, 1/8NMR, 13C NMR, and elemental analysis.
12. Camps, F.; Sanchez, F-J.; Messeguer, A. synthesis 1988, 823.
13. B6gu6, J.P.; Bonnet-Delpon, D.; Mesureur, D.; N6e, G.; Wu S.W. J. Org. Chem. 1992, 57, 3807.
14. Bey, P; Fozard, J.; Lacoste, J.M.; McDonald, I.A.; Zreika, M.; Palfreyman, M.G. J.Med. Chem. 1984,27, 9
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