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PROCESS FOR THE PREPARATION OF AMINO ACID DERIVATIVE

IP.com Disclosure Number: IPCOM000218123D
Publication Date: 2012-May-22
Document File: 3 page(s) / 54K

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The IP.com Prior Art Database

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PROCESS FOR THE PREPARATION OF AMINO ACID DERIVATIVE

    (R)-2-acetamido-N-benzyl-3-methoxy-propionamide, referred to as 'Compound VII', has the following formula,

Described hereinafter, is a process for the preparation of Compound VII. The process can be illustrated by the following scheme:


Page 02 of 3

    For the purpose of clarity and as an aid in the understanding of the disclosed process herein, the following terms and abbreviations are defined below:

Compound I Methyl 2-(benzyloxycarbonylamino)-3-hydroxyacrylate

Compound II Methyl 2-(benzyloxycarbonylamino)-3-methoxyacrylate

Compound III (R)-Methyl 2-(benzyloxycarbonylamino)-3-methoxypropanoate

Compound IV (R)-2-(Benzyloxycarbonylamino)-3-methoxypropanoic acid

    Compound V (R)-Benzyl 1-(benzylamino)-3-methoxy-1-oxopropan-2- ylcarbamate

Compound VI (R)-2-Amino-N-benzyl-3-methoxypropanamide

Compound VII (R)-2-Acetamido-N-benzyl-3-methoxypropanamide

The compounds of Formulae II and III can be characterized by data such as NMR or MS .

The above process comprises:


1. Etherification the compound of formula I to obtain the compound of formula II.

2. Asymmetric hydrogenating the compound of formula II to obtain the compound of formula III.


3. Hydrolyzing the compound of formula IV to obtain the compound of formula IV.


4. Amidation the compound of formula IV to obtain the compound of formula V.


5. Deprotecting the compound of formula V to obtain the compound of formula VI.


6. Acylating the compound of formula VI to obtain the compound of formula VII.

   The compound of formula I can be prepared for example by the procedure disclosed US 7,507,738 Examples I and II.

   The etherification of step 1, can be done for example by reacting the compound of formula I with sodium methoxide in the presence of dimethyl sulfate and dimethylformamide.

The compou...