Facile synthesis of a o-nitrobenzyl photolabile linker for combinatorial chemistry

Tetrahedron Letters

Volumn 37, Issue 32, 1996, Pages 5751-5754

  Teague, Simon J ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BUTYRIC ACID DERIVATIVE; PHENOXYBUTYRIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; PHOTOSYNTHESIS;

PUFFINUS AURICULARIS;

EID: 0030570849     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01175-6     Document Type: Article

References (15)

1. 1. Pillai, V. N. R., Synthesis (1980), 1-26.
2. 2. Terrett, N. K., Gardner, M., Gordon, D. W., Kobylecki, R. J. and Steele, J., Tetrahedron (1995), 51(30), 8135-8173.
3. 3. Holmes, C. P. and Jones, D. G., J. Org. Chem. (1995), 60, 2318-2319. For similar work see; Wilcox, M., Viola, R. W., Johnson, K. W., Billington, A. P., Carpenter, B. K., McCray, J. A., Guzikowski, A. P. and Hess, G. P., J. Org. Chem. (1990), 55, 1585-1589.
4. 3. Holmes, C. P. and Jones, D. G., J. Org. Chem. (1995), 60, 2318-2319. For similar work see; Wilcox, M., Viola, R. W., Johnson, K. W., Billington, A. P., Carpenter, B. K., McCray, J. A., Guzikowski, A. P. and Hess, G. P., J. Org. Chem. (1990), 55, 1585-1589.
5. 4. The synthesis of a very close analogue of (4) is described in outline in the patent liturature, but with limited detail. Holmes, C. P. WO9600378. The author is informed that such nitrations are possible and were the successful route used in the patent. The author wishes to thank the referee for his comments upon this reaction.
6. 5. Simpson, J. C. E., J. Chem. Soc. (1946), 94-97.
7. 6. Venkatesan, H. and Greenberg, M. M. J. Org. Chem. (1996), 61, 525-529. Also see Rogers, C. B., Blum, C. A. and Murphy, B. P., J. Heterocyclic Chem. (1987), 24, 941-943. and Murphy, B. P. J. Org. Chem. (1985), 50, 5873-5875.
8. 6. Venkatesan, H. and Greenberg, M. M. J. Org. Chem. (1996), 61, 525-529. Also see Rogers, C. B., Blum, C. A. and Murphy, B. P., J. Heterocyclic Chem. (1987), 24, 941-943. and Murphy, B. P. J. Org. Chem. (1985), 50, 5873-5875.
9. 6. Venkatesan, H. and Greenberg, M. M. J. Org. Chem. (1996), 61, 525-529. Also see Rogers, C. B., Blum, C. A. and Murphy, B. P., J. Heterocyclic Chem. (1987), 24, 941-943. and Murphy, B. P. J. Org. Chem. (1985), 50, 5873-5875.
10. 7. a) Weidmann, B. and Seebach, D. Angew. Chem. Int. Ed. Engl. (1983), 22, 31-45.
11. b) Fürstner, A., Jumbam, D. N. and Seidel, G. Chem. Ber., (1994), 127(6), 1125-1130.
12. 8. Experimental procedure: Potassium carbonate (10g, 72 mmol) was added to a solution of vanillin (10g, 66 mmol) and methyl 4-bromobutyrate (12g, 66 mmol) in DMF (80ml). The mixture was heated at 100°C for 1.5hrs, then poured into water (700ml), and extracted with ether. The extracts were washed with water, aq. hydrochloric acid, dried and evaporated to give a white solid. The crude product in methylene chloride (600ml) at -20°C was treated with fuming nitric acid (80ml). Upon completion (approx. 3hrs) the yellow mixture was poured into water (700ml) and extracted with methylene chloride. The extracts were washed with aq. sodium bicarbonate, dried and evaporated to give a yellow solid. The crude product was dissolved in dry methylene chloride (600ml) and treated dropwise at room temperature with trimethyl aluminium in hexanes (2M, 74 ml). Upon completion the reaction was poured into a beaker of ice cold aq. hydrochloric acid (700ml) [caution, foaming and methane evolved.] Extraction with methylene chloride, drying and evaporation gave a yellow solid which could be purified by crystallisation from 30% ethyl acetate in hexanes (approx 200ml).
13. 9. Imakura, Y., Okimoto, K., Konishi, T., Hisazumi, M., Yamazaki, J., Kobayashi, S. and Yamashita S., Chem. Pharm. Bull. (1992), 40(7), 1691-1696.
14. 2) solution of (8) (10g, 47 mmol) in DMSO (60ml) and methanol (30ml) at a rate sufficient to maintain reflux. [Caution hydrogen gas evolved]. Once the initial reaction had subsided the reaction was warmed at 80°C until complete (Tlc. 1:1 Ethyl acetate-hexanes). The excess methanoi was evaporated at reduced pressure and the mixture poured into aq. hydrochloric acid (2M, 800ml). Extraction with ethyl acetate, drying and evaporation gave the required compound (9) as a brown solid (7.3g).
15. 11. Cardno, M. and Bradley, M., Tet. Lett. (1996), 37(1), 135-138.