Process for the preparation of 4"-amino avermectin compounds

• US 5,362,863 A
• Filed: 09/29/1993
• Issued: 11/08/1994
• Est. Priority Date: 09/29/1993
• Status: Expired due to Term

• Current Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Original Assignee: Merck & Co., Inc.
• Inventors: Cvetovich, Raymond
• Primary Examiner(s): Brown, Johnnie R.
• Assistant Examiner(s): Lee, Howard C.
• Application Number:
  US08/128,936
• Time in Patent Office: 405 Days
• Field of Search: 536/7.1, 514/30, 514/450, 549/264
• US Class Current: 536/7.1
• CPC Class Codes: C07H 19/01 sharing oxygen

Abstract

A 4"-oxoavermectin intermediate is reductively aminated using hexa- or heptamethyldisilazane and sodium borohydride to produce a 4"-amino (or methylamino)avermectin. The 4"- aminoavermectin is a useful intermediate in the preparation of N-acyl derivatives. The compounds are useful as agricultural and animal health insecticides and parasiticides.

Claims

1. A process for the preparation of a compound of structural formula II ##STR11## wherein R³ is --NHR⁵, wherein R⁵ is --H or --CH₃ which comprises the steps of:

a) treating a compound of structural formula I ##STR12## with a compound of structural formula ##STR13## wherein R⁵ is --H or --CH₃ ; and

a Lewis acid selected from ZnCl₂, ZnBr₂ and Zn(OCOCF₃)₂ in an organic solvent selected from isopropylacetate, THF and toluene at a temperature of about 40°

to 60°

C.;

b) adding NaBH₄ in ethanol while keeping the temperature below 10°

C. during addition, to produce the compound of structural formula II a/d;

##STR14## where R³ is --NHR⁵, wherein R⁵ is --H or --CH₃ ; and

R⁴ is TMS; and

(c) treating IIa/d (R₁ =CO₂ CH₂ CH=CH₂)with (Ph₃ P)₄ Pd(O) and NaBH₄ in a C_1-3 alkanol at a temperature of about 5°

C. followed by treatment with a strong acid at about pH3;

or if R₁ =TBDMS, treating IIa/d with a strong acid at about pH3.