Large scale deprotection of a tert-butoxycarbonyl (Boc) group using aqueous HCl and acetone

Organic Process Research and Development

Volumn 8, Issue 6, 2004, Pages 945-947

  Coffey, D Scott ^a   Hawk, Mai Khanh N ^a   Pedersen, Steven W ^a   Ghera, Steven J ^a   Marler, Paul G ^a   Dodson, Paul N ^a   Lytle, Michelle L ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETONE; CARBONYL DERIVATIVE; CHLORIDE; GLUTAMATE RECEPTOR AGONIST; LY 544344;

AQUEOUS SOLUTION; ARTICLE; CONCENTRATION RESPONSE; CRYSTALLIZATION; DEPROTECTION REACTION; FILTRATION; MEDICAL LITERATURE; PROTON NUCLEAR MAGNETIC RESONANCE;

EID: 10044262122     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op049842z     Document Type: Article

References (7)

1. (a) Coffey, D. S.; Dantzig, A. H.; Hillgren, K. M.; Massey, S. M.; Moher, E. D.; Monn, J. A.; Pedersen, S. W.; Sweetana, S. A.; Valli, M. J.; Bueno Melendo, A. B.; De Dios, A.; Dominguez-Fernadez, C.; Herin, M. G.; Martin-Cabrejas, L. M.; Martin, J. A.; Martinez-Grau, M. A.; Montero Salgado, C.; Pedregal-Tercero, C. Preparation of Prodrugs of Excitatory Amino Acids. WO 0255485.
2. (b) Bueno Melendo, A. B.; Coffey, D. S.; Dantzig, A. H.; De Dios, A.; Dominguez-Fernadez, C.; Herin, M.; Hillgren, K. M.; Martin, J. A.; Martin-Cabrejas, L. M.; Martinez-Grau, M. A.; Massey, S. M.; Moher, E. D.; Monn, J. A.; Montero Salgado, C.; Pedersen, S. W.; Pedregal-Tercero, C.; Sweetana, S. A.; Valli, M. J. Preparation of Prodrugs of Excitatory Amino Acids. WO 0255481.
3. Stahl, G. L.; Walter, R.; Smith, C. W. J. Org. Chem. 1978, 43, 2285.
4. Compound 1 isolated from the deprotection reaction prior to recrystallization is referred to as technical grade 1.
5. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis; Wiley: New York, 1999.
6. Since this was the final step in the synthesis, only class 3 solvents as defined by ICH guidelines were considered. For more information, see: ICH Harmonised Tripartite Guideline, Impurities: Guidline for Residual Solvents, Q3C; July 1997.
7. Spiking studies confirmed that diacetone alcohol was converted to mesityl oxide under the reaction conditions.