Process for the synthesis of cyclic carbamates

摘要

The invention is directed to a process for the preparation of a cyclic carbamate starting with a chiral propargylic alcohol and/or a suitable salt thereof, which is reacted with a cyclization agent selected from phosgene, diphosgene, triphosgene and mixtures thereof, and in that the reaction is carried out in the presence of an aqueous base, and a water-immiscible organic solvent, said organic solvent mainly comprising at least one compound selected from C2-5-alkyl C2-5-carboxylates and mixtures of at least one C2-5-alkyl C2-5-carboxylate with at least one C5-8-alkane. Another aspect of the invention is directed to a process for the synthesis of said cyclic carbamate starting described above, wherein also a process for the preparation of the chiral propargylic alcohol is provided.

主权项

1. A process for the preparation of a compound of formula and/or a suitable salt thereof, wherein R1 is selected from the group consisting of hydrogen, linear or branched C1-6-alkyl or (C1-6-alkoxy)carbonyl, any alkyl or alkoxy optionally being substituted with one or more halogen atoms, R2 is selected from the group consisting of linear or branched C1-6-alkyl, (C1-6-alkoxy)carbonyl, C3-6-alkenyl, C3-6-alkynyl and C3-6-cycloalkyl, wherein each alkyl, alkoxy, alkenyl, alkynyl and cycloalkyl can carry a further substituent selected from the group consisting of aryl, aralkyl, C1-6-alkyl and (1′-R3)—C3-6-cycloalkyl, wherein R3 is hydrogen, methyl or ethyl, and wherein any alkyl, cycloalkyl, aryl, and aralkyl is optionally substituted with one or more halogen atoms, cyano, C1-6-alkyl, C3-6-cycloalkyl, —NR4R5, —SR6, S(O) R6 or S(O2)R6, and/or —OR7, with R6 is C1-6-alkyl, optionally substituted with one or more halogen atoms, R7 is hydrogen or C1-6-alkyl, optionally substituted with one or more halogen atoms, where (a) R4 and R5 are independently selected from hydrogen or C1-6-alkyl, or (b) R4 is hydrogen and R5 is C2-7-acyl or (C1-6-alkoxy)carbonyl, wherein each acyl and alkoxy in R5 in turn is optionally substituted with one or more halogen atoms, or (c) R4 and R5 together with the nitrogen atom form a 5 to 7 membered heterocyclic ring, or (d) R4 and R5 together are ═CH-aryl, the aryl moiety optionally being substituted with one or more substituents selected from halogen atoms, —NH2, —NH(C1-6-alkyl), —N(C1-6-alkyl)2 or C1-6-alkyl, or (e) R4 and R5 together are ═CH—N(C1-6-alkyl)2, R6 is C1-6-alkyl, optionally substituted with one or more halogen atoms, and R7 is hydrogen or C1-6-alkyl, optionally substituted with one or more halogen atoms, R8 and R9 are independently selected from the group consisting of hydrogen, halogen atom, and C1-6-alkyl optionally substituted with one or more halogen atoms, R10 is hydrogen or a group selected from the group consisting of aryl, aralkyl, C1-6-alkyl and (C1-6-alkoxy)carbonyl, wherein the aryl moiety in any aryl or aralkyl is optionally substituted with one or more substituents selected from C1-6-alkyl, C1-6-alkoxy or C1-6-cycloalkyl, each alkyl, alkoxy or cycloalkyl substituent is optionally substituted with one or more halogen atoms, said process comprising the reaction of a compound of formula and/or a suitable salt thereof, wherein R1, R2, R8, R9 and R10 are as defined above, with a cyclisation agent selected from phosgene, diphosgene, triphosgene and mixtures thereof, wherein the reaction is carried out in the presence of an aqueous base and a water-immiscible organic solvent, wherein at least 90% of said organic solvent consists of at least one compound selected from the group consisting of C2-5-alkyl C2-5-carboxylates and mixtures of at least one C2-5-alkyl C2-5-carboxylate with at least one C5-8-alkane.