Solid phase synthesis of aryl amines

Tetrahedron Letters

Volumn 37, Issue 40, 1996, Pages 7181-7184

  Willoughby, Christopher A ^a   Chapman, Kevin T ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANILINE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS; TECHNIQUE;

EID: 0030607186     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01633-4     Document Type: Article

References (14)

1. 1. Dankwardt, S. M.; Newman, S. R.; Krstenansky, J. L. Tetrahedron Lett. 1995, 36, 4923.
2. 2. a) Kosugi, M.; Kameyama, M.; Migita, T. Chem. Lett. 1983, 927.
3. b) Paul, P.; Patt, J.; Hartwig, J. F. J. Am. Chem. Soc. 1994, 116, 5969.
4. c) Luoie, J.; Hartwig, J. F. Tetrahedron Lett. 1995, 36, 3609.
5. d) Guram, A. S.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 7901.
6. e) Guram, A. S.; Rennels, R. A.; Buchwald, S. L. Angew. Chem. Int. Ed. Engl. 1995, 34, 1348.
7. 3. Aryl bromides were attached through a carboxamide link by coupling of the approriate acid derivative using EDC / DMF.
8. 4. Aryl bromides were attached through a urea link using the method previously reported. Hutchins, S. M.; Chapman, K. T. Tetrahedron Lett. 1994, 35, 4055.
9. 2 and AcOH (4×2mL each). The products were cleaved by treatment of the resin with 90 % TFA/water for 20 min (2 ×). The sample was concentrated and lyophilized from acetic acid.
10. 6. Analysis by HPLC using a 4×100 mm Zorbax SB-C8 column (5μ particle size) with a gradient of 10% acetonitrile/water containing 0.1 % TFA to 100 % acetonitrile over 10 min. Peak areas were integrated at 220 nm.
11. 7. While this work was in progress a similar observation was reported for the solution phase coupling reaction; Hartwig, J. F.; Richards, S,; Baranano, D.; Paul, F. J. Am. Chem. Soc. 1996, 118, 3626.
12. 2O in dioxane followed by coupling under standard conditions no isotope incorporation was observed. These results indicate that reduction through participation of solvent or adventitious moisture is not occuring.
13. 9. R. H. Crabtree, "The Organometallic Chemistry of the Transition Metals" John Wiley and Sons, New York, pp. 154-159.
14. 10. Similar results have been observed in the solution phase reaction; Buchwald, S. L. personal communication. Other chelating ligands such as bisdiphenylphosphinopropane or bisdiphenylphosphinoethane were ineffective in the present work.