Patent EA-002777-B1 (EA)
Title: Process for preparing hydroxamic acid
Inventor: HAWKINS JOEL MICHLE
IPC: C07C311/29
Filed: 1999-04-09
Abstract: 1. A process for preparing a compound of the formula   Z is >CH2 or >NR<1>; Q is (C1 -C6)alkyl, (C6 -C10)aryl, (C2 -C9)heteroaryl, (C6 -C10)aryloxy(C1 -C6)alkyl, (C6 -C10)aryloxy(C6 -C10)aryl, (C6 -C10)aryloxy(C2 -C9)heteroaryl, (C6 -C10)aryl(C1 -C6)alkyl, (C6 -C10)aryl(C6 -C10)aryl, (C6 -C10)aryl(C2 -C9)heteroaryl, (C6 -C10)aryl(C6 -C10)aryl(C1 -C6)alkyl, (C6 -C10)aryl(C6 -C10)aryl(C6 -C10)aryl, (C6 -C10)aryl(C6 -C10)aryl(C2 -C9)heteroaryl, (C2 -C9)heteroaryl(C1 -C6)alkyl, (C2 -C9)heteroaryl(C6 -C10)aryl, (C2 -C9)heteroaryl(C2 -C9)heteroaryl, (C6 -C10)aryl(C1 -C6)alkoxy(C1 -C6)alkyl, (C6 -C10)aryl(C1 -C6)alkoxy(C6 -C10)aryl, (C6 -C10)aryl(C1 -C6)alkoxy(C2 -C9)heteroaryl, (C2 -C9)heteroaryloxy(C1 -C6)alkyl, (C2 -C9)heteroaryloxy(C6 -C10)aryl, (C2 -C9)heteroaryloxy(C2 -C9)heteroaryl, (C2 -C9)heteroaryl(C1 -C6)alkoxy(C1 -C6)alkyl, (C2 -C9)heteroaryl(C1 -C6)alkoxy(C6 -C10)aryl or (C2 -C9)heteroaryl(C1 -C6)alkoxy(C2 -C9)heteroaryl; wherein each (C6 -C10)aryl or (C2 -C9)heteroaryl moieties of said (C6 -C10)aryl, (C2 -C9)heteroaryl, (C6 -C10)aryloxy(C1 -C6)alkyl, (C6 -C10)aryloxy(C6 -C10)aryl, (C6 -C10)aryloxy(C2 -C9)heteroaryl, (C6 -C10)aryl(C1 -C6)alkyl, (C6 -C10)aryl(C6 -C10)aryl, (C6 -C10)aryl(C2 -C9)heteroaryl, (C6 -C10)aryl(C6 -C10)aryl(C1 -C6)alkyl, (C6 -C10)aryl(C6 -C10)aryl(C6 -C10)aryl, (C6 -C10)aryl(C6 -C10)aryl(C2 -C9)heteroaryl, (C2 -C9)heteroaryl(C1 -C6)alkyl, (C2 -C9)heteroaryl(C6 -C10)aryl, (C2 -C9)heteroaryl(C2 -C9)heteroaryl, (C6 -C10)aryl(C1 -C6)alkoxy(C1 -C6)alkyl, (C6 -C10)aryl(C1 -C6)alkoxy(C6 -C10)aryl, (C6 -C10)aryl(C1 -C6)alkoxy(C2 -C9)heteroaryl, (C2 -C9)heteroaryloxy(C1 -C6)alkyl, (C2 -C9)heteroaryloxy(C6 -C10)aryl, (C2 -C9)heteroaryloxy(C2 -C9)heteroaryl, (C2 -C9)heteroaryl(C1 -C6)alkoxy(C1 -C6)alkyl, (C2 -C9)heteroaryl(C1 -C6)alkoxy(C6 -C10)aryl or (C2 -C9)heteroaryl(C1 -C6)alkoxy(C2 -C9)heteroaryl  is optionally substituted on any of the ring carbon atoms capable of forming an additional bond by one or more substituents per ring independently selected from fluoro, chloro, bromo, (C1 -C6)alkyl, (C1 -C6)alkoxy, perfluoro(C1 -C3)alkyl, perfluoro(C1 -C3)alkoxy and (C6 -C10)aryloxy; R<1> is hydrogen, (C1 -C6)alkyl, (C6 -C10)aryl(C1 -C6)alkyl, (C2 C9)heteroaryl(C1 -C6)alkyl group of the formula   wherein R<2> and R<3> are independently hydrogen, (C1 -C6)alkyl or R<2> and R<3> are taken together to form a three to seven membered cycloalkyl ring, a pyran-4-yl ring or a bicyclo ring of the formula   wherein the asterisk indicates the carbon atom common to R<2> and R<3> ; and R<4> is (C1 -C6)alkyl; n is an integer from one to six; comprising: a) reacting hydroxylamine, or a salt thereof, with a ((C1 -C6)alkyl)3 silyl halide in the presence of a first base, to form an in situ ((C1 -C6)alkyl)3 silylated hydroxylamine, b) reaction of said in situ ((C1 -C6)alkyl)3 silylated hydroxylamine with a compound of the formula   wherein R<2>, R<3>, Z and Q are as defined above, with a second base to form a compound of the formula   wherein R<7> is ((C1 -C6)alkyl)3 --Si--, and R<8> is hydrogen or ((C1 -C6)alkyl)3 --Si--; and c) hydrolysis of said compound of formula VI with an acid. 2. A process according to claim 1, wherein said first base is pyridine, 2,6-lufidirie or diisopropylethylamine. 3. A process according to claim 1, wherein said first base is pyridine. 4. A process according to claim 1, wherein said ((C1 -C6)alkyl)3 silyl halide is trimethyl silyl chloride. 5. A process according to claim 1, wherein said second base is pyridine, 2,6-lutidine or diisopropylethylamine. 6. A process according to claim 1, wherein said second base is pyridine.