Synthesis of enantiopure (R)-2-(4-methoxy-3-(3-methoxypropoxy)-benzyl)-3-methylbutanoic acid-a key intermediate for the preparation of Aliskiren

Tetrahedron Letters

Volumn 49, Issue 41, 2008, Pages 5980-5982

  Andrushko, Natalia ^a   Andrushko, Vasyl ^a   Thyrann, Thomas ^b   König, Gerd ^c   Börner, Armin ^a,d  

^a LEIBNIZ INSTITUT FÜR KATALYSE E V AN DER UNIVERSITÄT ROSTOCK   (Germany)

^b Ratiopharm Schweiz AG   (Switzerland)

^c ratiopharm GmbH   (Germany)

^d UNIVERSITY OF ROSTOCK   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

2 [4 METHOXY 3 (3 METHOXYPROPOXY)BENZYL] 3 METHYLBUTANOID ACID; 2 [4 METHOXY 3 (3 METHOXYPROPOXY)BENZYLIDENE] 3 METHYLBUTANOID ACID; ALISKIREN; BUTYRIC ACID; CARBOXYLIC ACID; UNCLASSIFIED DRUG;

ARTICLE; CATALYSIS; CHEMICAL STRUCTURE; ENANTIOMER; ENANTIOSELECTIVITY; ENZYME SUBSTRATE; HYDROGENATION; STEREOCHEMISTRY;

EID: 50049135157     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2008.07.150     Document Type: Article

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15. 2, the solvent was evaporated and 2-(4-methoxy-3-(3-methoxypropoxy)-benzyl)-3-methylbutanoic acid (95% ee) was obtained.
16. A similar method was applied in a preparative scale for the purification of R-(-)-ibuprofen:. Trung T.Q., Kim J.M., and Kim K.H. Arch. Pharm. Res. 29 (2006) 108-111
17. To the solution of acid 2 (95% ee) (235 mg, 0.76 mmol) in 3 ml of diethyl ether was added at room temperature dropwise a solution of (S)-(-)-α-methyl benzylamine (96.3 mg, 0.8 mmol) in 2 ml of diethyl ether. The solution was cooled and allowed to stand in the fridge overnight. Crystals formed were filtered off and dried.
18. 4, filtered off, and evaporated.