02-03-2017 дата публикации
Номер: US20170057937A1
Принадлежит:
The invention relates to a process for the preparation of Efavirenz via an efficient transition metal catalyzed cyclization, to a device suitable to perform such process as well as to novel intermediates. 1. A process for the preparation of 6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1H-3 ,1-benzoxazin-2-one comprising reacting 4-cyclopropyl-2-(2 ,5-dichloro-phenyl)-1 ,1 ,1-trifluoro-but-3-yn-2-ol with at least one cyanate in the presence of at least one transition metal compound.2. The process according to claim 1 , wherein the at least one cyanate is selected from the group consisting of alkali cyanates and alkaline earth cyanates.3. The process according to claim 1 , wherein the at least one cyanate comprises sodium cyanate.4. The process according to claim 1 , wherein the at least one transition metal compound is selected from the group consisting of copper claim 1 , nickel claim 1 , palladium claim 1 , rhodium and platinum compounds.5. The process according to claim 1 , wherein the at least one transition metal compound is selected from those of formulae (Ia) and (Ib){'br': None, 'sup': '1', 'sub': '2', 'M(Y)\u2003\u2003(Ia),'}{'br': None, 'sup': '2', 'M(Y)\u2003\u2003(Ib),'}whereinM is nickel, palladium or copper(II){'sup': '1', 'Yis chloride, bromide, acetate, nitrate, methanesulphonate, trifluoromethanesulphonate, trifluoroacetate or acetylacetonate, and'}{'sup': '2', 'Yis sulphate;'} [{'br': None, 'sup': '3', 'MY\u2003\u2003(IIa)'}, {'br': None, 'sub': '4', 'sup': '3', '[M(B)](Y)\u2003\u2003(IIb)'}], 'or those of formulae (IIa) and (IIb)'}whereinM is copper (I){'sup': '3', 'Yis chloride, bromide, iodide, acetate, methanesulphonate, trifluoromethanesulphonate, tetrafluoroborate, trifluoroacetate hexafluorophosphate, perchlorate, hexafluoroantimonate, tetra(3,5-bistrifluoromethylphenyl)borate or tetraphenylborate, and'}B is a nitrile such as acetonitrile, benzonitrile, benzyl nitrile; {'br': None, 'sub': '2', '[M(D)]\u2003\u2003(III)'}, 'or those of ...
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