Method for preparing .omega.-aminoalkanoic acid derivatives from cycloalkanones

• US 6,084,112 A
• Filed: 12/15/1997
• Issued: 07/04/2000
• Est. Priority Date: 09/11/1995
• Status: Expired due to Term

• Current Assignee: NOVO Nordisk North America Operations A/S
• Original Assignee: Emisphere Technologies, Inc. (Novo Nordisk A/S)
• Inventors: Ho, Koc-Kan, Leone-Bay, Andrea
• Primary Examiner(s): Carr, Deborah D.
• Application Number:
  US08/894,490
• Time in Patent Office: 932 Days
• Field of Search: 584/114
• US Class Current: 554/114
• CPC Class Codes: C07C 227/22 from lactams, cyclic ketones or cyclic oximes, e.g. by reactions involving Beckmann rearrangement
• CPC Class Codes: C07C 269/04 from amines with formation of carbamate groups
• CPC Class Codes: C07C 271/22 to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
• CPC Class Codes: C07K 5/021 containing the structure -NH-(X)n-C(=0)-, n being 5 or 6; for n > 6, classification in C07K5/06 - C07K5/10, according to the moiety having normal peptide bonds

Abstract

A convenient synthetic route to ω-aminoalkanoic acids, N-Boc protected ω-aminoalkanoic acids and Boc-amino acid coupled ω-aminoalkanoic acids is disclosed. The method provides high purity compounds that generally do not require further purification.

Claims

1. A method for preparing a compound having the formula ##STR8## said method comprising:

(a) reacting a cycloalkanone compound having the formula;

##STR9## with formic acid an hydroxylamine-O-sulfonic acid to provide a lactam having the formula;

##STR10## (b) reacting said lactam with an aqueous base to form an amine salt; and

(c) acylating said amine salt with a compound having the formula;

##STR11## or a Boc protected amino acid succinate ester;

wherein

Y is carbonyl or oxycarbonyl;

Z is a bond or an amino acid residue;

R¹ is C₅ -C₉ alkyl;

R² is hydrogen;

R³ is tert-butyl or hydroxyphenyl;

R⁴ is hydrogen; and

X is a leaving group.

2. The method according to claim 1, wherein the amine salt is acylated with a compound having the formula (CH₃)₃ C--O--CO--X, wherein X is a halide.

3. The method according to claim 1, wherein the amine salt is acylated with a compound having the formula ((CH₃)₃ C--O--CO)₂ O.

4. The method according to claim 1, wherein the amine salt is acylated with a Boc protected amino acid succinate ester.

5. The method according to claim 4, wherein the amine salt is acylated with Boc-phenyl alanyl-O-succinate ester.

6. The method according to claim 4, wherein the amine salt is acylated with Boc-phenyl alanyl-phenyl alanyl-O-succinate ester.

7. The method according to claim 1, wherein R1 is alkyl having 6 carbon atoms, Z is a bond, Y is carbonyl, and R³ is 2-hydroxyphenyl.