A new cleavage strategy for the solid-phase synthesis of secondary amines

Tetrahedron Letters

Volumn 38, Issue 16, 1997, Pages 2915-2918

  Conti, Paolo ^a   Demont, Dennis ^a   Cals, Jos ^a   Ottenheijm, Harry C J ^a   Leysen, Dirk ^a  

^a NV ORGANON   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

AMINE;

ARTICLE; DRUG SYNTHESIS; IN VITRO STUDY; METHODOLOGY; REACTION ANALYSIS; TECHNIQUE;

EID: 0030951330     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)00502-9     Document Type: Article

References (16)

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7. Morphy, J.R.; Rankovic, Z.; Rees, D.C. Tetrahedron Lett. 1996, 37, 3209-3212.
8. Olofson, R.A.; Martz, J.T.; Senet, J.-P.; Piteau, M.; Malfroot, T. J. Org. Chem. 1984, 49, 2081-2082.
9. Yang, B.V.; O'Rourke, D.; Jiancheng, L. Synlett 1993, 195-196.
10. Merrifield R.B.; J. Amer. Chem. Soc. 1963, 85, 2149-2154.
11. Wang S.-S.; J. Amer. Chem. Soc. 1973, 95, 1328-1333.
12. Mergler, M.; Tanner, R.; Gosteli, J.; Grogg, P. Tetrahedron Lett. 1988, 400-4008.
13. The substitution level was determined by measuring the remaining chloride contents by a Schöninger combustion followed by ion chromatography with conductivity detection
14. The solvent originally described for this type of reaction, e.g. 1,2-dichloroethane, was replaced by 1,2-dichloropropane, in view of the reported carcinogenic, mutagenic and teratogenic activities of the former. Dichloromethane could also be used successfully.
15. 9 who reported that in solution, treatment of piperazines bearing two different N-benzyl groups with ACE-Cl causes selective removal of one such group depending on electron-densities and sterical hindrance.
16. 2. The suspension was heated for 17 h at 80°C, cooled to room temperature, treated with 1 ml of ethanol and heated for 3h at 80°C. The resin was filtered off, washed with ethanol, ethanol/dichloromethane and dichloromethane and suspended in 1,2-dichloropropane. A total of 0.1 ml of α-chloroethyl chloroformate (ACE-Cl) was added and the resulting suspension was stirred at room temperature for 3 hours. The resin was filtered off and the filtrate evaporated to dryness. The residue was dissolved in methanol and the resulting solution was refluxed for 3 hours. The solvent was removed to yield 1-(2-aminomethylphenyl)piperazine dihydrochloride.