Preparation of amino acids and amino acid derivatives

Patent metadata

Field	Value
Publication number	US-10774035-B2
Application number	US-201716335342-A
Country	US
Kind code	B2
Filing date	Sep 6, 2017
Priority date	Sep 23, 2016
Publication date	Sep 15, 2020
Grant date	Sep 15, 2020

Abstract

The invention relates to a method for synthesizing amino acids or amino acid derivatives involving cross metathesis of functionalized olefins and a tandem amination-reduction process. Amino acids and amino acid derivatives present many interesting physical and chemical properties finding many uses in the automotive, fuel, electronic, and textile industries.

First claim

What is claimed is:

1. A process for synthesizing an amino acid or an amino acid derivative represented by the structure of Formula 1,

comprising the steps of:
(a) subjecting an olefinic substrate represented by the structure of Formula 2

to a cross metathesis reaction with a cross metathesis substrate represented by the structure of formula

in the presence of at least one metal carbene olefin metathesis catalyst, to form an unsaturated protected alcohol intermediate represented by the structure of Formula 2a

(b) subjecting the unsaturated protected alcohol intermediate represented by the structure of Formula 2a to hydrolysis in basic conditions to yield an unsaturated alcohol represented by the structure of Formula 3

and;
(c) converting the unsaturated alcohol represented by the structure of Formula 3, to an amino acid or an amino acid derivative represented by the structure of Formula 1, by subjecting the unsaturated alcohol represented by the structure of Formula 3 to a tandem amination-reduction, wherein the tandem amination-reduction is carried out in the presence of a Ruthenium pincer complex represented by the structure of Formula 4:

wherein: R is H, optionally substituted C 1 -C 12 alkyl, optionally substituted C 6 -C 10 aryl, optionally substituted heterocycle or optionally substituted C 5 -C 10 cycloalkyl;
R 1 is —H, —CH 3 or —COOR;
R 2 is —OR 3 ;
R 3 is optionally substituted CO(C 1 -C 12 alkyl), optionally substituted CO(C 5 -C 10 cycloalkyl), optionally substituted CO(C 6 -C 10 aryl), or optionally substituted CO(C 5 -C 10 heterocycle);
R 4 is —H or —(CH 2 ) m1 OR 3 ; R 5 is —(CH 2 ) m1 OR 3 ;
a is 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22;
m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19;
m 1 is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19;
p is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19;
L 4 and L 5 are each independently selected from the group consisting of phosphine (PR a R b ), amine (NR a R b ), imine, sulfide (SR d ), thiol (SH), sulfoxide (S(═O)R d ), heteroaryl containing at least one heteroatom selected from nitrogen and sulfur; arsine (AsR a R b ), stibine (SbR a R b ) and an N-heterocyclic carbene represented by the structures:

L 6 is a mono-dentate two-electron donor selected from the group consisting of CO, PR a R b R c , NO + , AsR a R b R c , SbR a R b R c , SR a R b , nitrile (R d CN), isonitrile (R d NC), N 2 , PF 3 , CS, heteroaryl, tetrahydrothiophene and N-heterocyclic carbene;
R 6 and R 7 are either each hydrogen or together with the carbons to which they are attached represent a phenyl ring which is fused to the quinolinyl moiety represented by the structure of Formula 4 so as to form an acridinyl moiety;
R a , R b , R c , R d , R 8 , R 9 and R 10 are each independently alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl or alkylheteroaryl;
Y a is a monoanionic ligand selected from the group consisting of halogen, OCOR d , OCOCF 3 , OSO 2 R d , OSO 2 CF 3 , CN, OH, OR d , NR d 2 ; a neutral solvent molecule NH 3 , NR 3 and R d 2 NSO 2 R d , and when Y a is neutral, the whole molecule carries a positive charge;
X a represents one, two, three, four, five, six or seven substituents positioned at any carbon atom on the acridinyl moiety, or in the case where R 6 and R 7 together with the carbons to which they are attached represent a phenyl ring which is fused to the quinolinyl moiety represented by the structure of Formula 4; or one, two, three, four or five substituents positioned on any carbon atom on the quinolinyl moiety, or in the case where R 6 and R 7 are each hydrogen, and is selected from the group consisting of hydrogen, alkyl, aryl, heterocyclyl, heteroaryl, alkylcycloalkyl, alkylaryl, alkylheterocyclyl, alkylheteroaryl, halogen, nitro, amide, ester, cyano, alkoxy, alkylamino, arylamino, an inorganic support and a polymeric moiety; and with the proviso that the sum of any combination of m 1 and p is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

2. The process according to claim 1 , wherein the at least one metal carbene olefin metathesis catalyst is a Group 8 transition metal complex.

3. The process according to claim 1 , wherein the tandem amination-reduction is further carried out in the presence of ammonia and hydrogen.

4. The process according to claim 1 , wherein the cross metathesis substrate represented by the structure of formula

is 1,4-diacetoxy-2-butene.

5. The process according to claim 4 , wherein the Ruthenium pincer complex represented by the structure of Formula 4 is Chlorocarbonylhydrido[4,5-bis-(di-i-propylphosphinomethyl)acridine] Ruthenium (II) or Chlorocarbonylhydrido[4,5-bis-(di-cyclohexylphosphinomethyl)acridine] Ruthenium (II).

6. The process according to claim 1 , wherein R is H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 6 aryl, or optionally substituted C 5 -C 10 cycloalkyl; R 1 is —H, —CH 3 or —COOR; R 2 is —OR 3 ; R 3 is optionally substituted CO(C 1 -C 6 alkyl), optionally substituted CO(C 5 -C 10 cycloalkyl), optionally substituted CO(C 6 aryl); R 4 is —H or —(CH 2 ) m1 OR 3 ; R 5 is —(CH 2 ) m1 OR 3 ; a is 6, 7, 8, 9, 10, 11, 12, 13, 14, 15; 16 or 17; m is 0, 1, 2, 3, 4, 5, 6, or 7; m 1 is 1, 2, or 3; p is 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; and with the proviso that the sum of any combination of m 1 and p is 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15.

7. The process according to claim 6 , wherein R is H, optionally substituted C 1 -C 3 alkyl; R 1 is —H, —CH 3 or —COOR; R 2 is —OR 3 ; R 3 is optionally substituted CO(C 1 -C 3 alkyl); R 4 is —H or —(CH 2 ) m1 OR 3 ; R 5 is —(CH 2 ) m1 OR 3 ; a is 9, 10, 11 or 12; m is 0, 1, 2, 3, 4, 5, 6 or 7; m 1 is 1 or 2; p is 6, 7 or 8.

8. The process according to claim 6 , wherein R is CH 3 ; R 1 is H, CH 3 or COOR; R 2 is OR 3 ; R 3 is CH 3 (CO)—; a is 9, 10, 11 or 12; m is 0, 1, 2, 3, 4, 5, 6 or 7; m 1 is 1 or 2; p is 6, 7 or 8; and the cross metathesis substrate represented by the structure of formula

is 1,4-diacetoxy-2-butene.

9. The process according to claim 8 , wherein a is 10; m is 0; m 1 is 1; and p is 7.

10. The process according to claim 8 , wherein a is 11; m is 0; m 1 is 1; and p is 8.

11. The process according to claim 1 , wherein: the cross metathesis substrate represented by the structure of formula

Assignees

• Umicore Ag & Co Kg

Inventors

• Johns Adam M
• Herron Jessica R
• Pederson Richard L
• Ung Thay A
• Tran Ba L
• Allen Daryl P

Classifications

• B01J31/2265

  Carbenes or carbynes, i.e.(image) · CPC title

• B01J31/2278

  Complexes comprising two carbene ligands differing from each other, e.g. Grubbs second generation catalysts · CPC title

• B01J2231/349

  1,2- or 1,4-additions in combination with further or prior reactions by the same catalyst, i.e. tandem or domino reactions, e.g. hydrogenation or further addition reactions · CPC title

• B01J31/0244

  with nitrogen contained as ring member in aromatic compounds or moieties, e.g. pyridine · CPC title

• C07C227/08 Primary

  by reaction of ammonia or amines with acids containing functional groups · CPC title