Solid phase synthesis of substituted coumarin-3-carboxylic acids via the Knoevenagel condensation

Tetrahedron Letters

Volumn 39, Issue 33, 1998, Pages 6087-6090

  Watson, Brett T ^a   Christiansen, Gerda E ^a  

^a NOVO NORDISK A S   (Denmark)

Author keywords

Combinatorial chemistry; Coumarins; Knoevenagel condensation; Solid phase synthesis

Indexed keywords

CARBOXYLIC ACID DERIVATIVE; COUMARIN DERIVATIVE;

ARTICLE; CHEMICAL INDUSTRY; DRUG INDUSTRY; DRUG SYNTHESIS; POLYMERIZATION; SOLID PHASE EXTRACTION;

EID: 0032514516     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)01255-6     Document Type: Article

References (8)

1. 1. Zaragoza, F. Tetrahedron Lett. 1995, 36, 8677-8678.
2. 2. (a) Hamper, B.C.; Kolodziej, S.A.; Scates, A.M. Tetrahedron Lett. 1998, 39, 2047-2050;
3. (b) Whitehouse, D.L.; Nelson Jr., K.H.; Savinov, S.N.; Austin, D.J. Tetrahedron Lett. 1997, 38, 7139-7142.
4. 3. Gordeev, M.F.; Patel, D.V.; Wu, J.; Gordon, E.M. Tetrahedron Lett. 1996, 37, 4643-4646.
5. 4. Jones, G The Knoevenagel Condensation. In: Adams, R. editor. Organic Reactions, vol. 15, New York: John Wiley and Sons, 1967: 204-599.
6. 2 (1/2) and shaken for 1 h. The reaction was filtered, the resin washed with methylene chloride (2x) and the filtrate was evaporated to give product.
7. 6. Using the same synthetic method as described in note 5, in two independent experiments, 2-methoxybenzaldehyde and 2,3-methylenedioxybenzaldehyde were allowed to react with Wang resin-bound methyl malonate. After cleavage, 1.4:1 and 1.6:1 mixtures of the E/Z isomers were obtained in 61%, 83% yield respectively; both with 94% purity as measured by HPLC (254 run).
8. 7. 2-hydroxybenzaldehyde, ethyl-3-coumarin carboxylate, and coumarin-3-carboxylic acid were correlated by HPLC retention times with authentic samples.