An improved synthesis of N-isocyanoiminotriphenylphosphorane and its use in the preparation of diazoketones

Synthesis

Volumn , Issue 1, 2005, Pages 19-21

  Bio, Matthew M ^a   Javadi, Gary ^a   Song, Zhiguo Jake ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Diazoketone; Diazomethane; Iminophosphorane; Isonitrile

Indexed keywords

KETONES; METHANE;

DIAZOKETONES; DIAZOMETHANE; N-ISOCYANOIMINOTRIPHENYLPHOSPHORANE;

SYNTHESIS (CHEMICAL);

BASE; DIAZOKETONE; DIAZOMETHANE; ISONITRILE DERIVATIVE; KETONE DERIVATIVE; N ISOCYANOIMINOTRIPHENYLPHOSPHORANE; PHOSPHORANE DERIVATIVE; REAGENT; SOLVENT; UNCLASSIFIED DRUG;

ARNDT EISTERT SYNTHESIS; ARTICLE; CHEMICAL REACTION; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; SYNTHESIS; TEMPERATURE;

EID: 12344335218     PISSN: 00397881     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2004-834928     Document Type: Article

References (19)

1. Arndt, F.; Eistert, B. Chem. Ber. 1935, 68, 200.
2. (a) Aoyama, T.; Shioiro, T. Tetrahedron Lett. 1980, 21, 4461.
3. (b) Aoyama, T.; Shioiro, T. Chem. Pharm. Bull. 1981, 29, 3249.
4. Proctor, L. D.; Warr, A. J. Org. Process Res. Dev. 2002, 6, 884; and references therein.
5. Aller, E.; Molina, P.; Lorenzo, Á. Synlett 2000, 526.
6. It should be noted that diazoketones themselves are often unstable compounds, thus great care should be taken whenever diazoketones or diazoalkanes are being formed.
7. 2 is used.
8. (a) Aller and co-workers reference the following paper for the synthesis of 1: Weinberger, B.; Fehlhammer, W. P. Chem. Ber. 1985, 118, 42.
9. (b) To the best of our knowledge no other syntheses of 1 have been reported.
10. 4 in detail and notes the acceleration of the reaction in MeCN specifically: Appel, R. Angew. Chem., Int. Ed. Engl. 1975, 14, 801.
11. 3 (1:1) aqueous solution.
12. The addition of more water anti-solvent led to high isolated yield but lower quality material.
13. The synthesis of 6 will be published at a later date.
14. 4 and DBU give a raw material cost of $0.54/gram N-isocyanotriphenyliminophosphorane.
15. For a review see: Ye, T.; McKervey, A. Chem. Rev. 1994, 94, 1091.
16. 4,6 we have found only a single additional mention of this compound in the literature: Zinner, G.; Beck, G.; Fehlhammer, W. P.; Wilberg, N. J. Organomet. Chem. 1989, 368, 23.
17. Adding seed to the reaction is necessary only if no crystalline material has precipitated upon cooling to 35°C. The initial seed may be obtained by removing a few millilitres of the reaction solution and cooling it to r.t.
18. After 40 min the reaction was complete by HPLC assay; a reaction sample quenched into MeOH show ca 99% conversion to the methyl ester.
19. Concentration and flush with fresh DCE removes excess oxalyl chloride.