Aqueous phosphoric acid as a mild reagent for deprotection of the t-butoxycarbonyl group

Tetrahedron Letters

Volumn 44, Issue 44, 2003, Pages 8113-8115

  Li, Bryan ^a   Bemish, Raymond ^a   Buzon, Richard A ^a   Chiu, Charles K F ^a   Colgan, Stephen T ^a   Kissel, William ^a   Le, Tung ^a   Leeman, Kyle R ^a   Newell, Lisa ^a   Roth, Joshua ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

BOC; Deprotection; Phosphoric acid

Indexed keywords

ALKENE DERIVATIVE; BENZYL DERIVATIVE; CARBONYL DERIVATIVE; ETHER DERIVATIVE; METHYL GROUP; PHOSPHORIC ACID; REAGENT;

ACIDITY; AQUEOUS SOLUTION; ARTICLE; DEPROTECTION REACTION; SENSITIZATION;

EID: 0141571021     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2003.09.040     Document Type: Article

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21. 4 were used.
22. It is possible to heat the reaction to accelerate the reaction to reduce the amount of reagent used when no other acid sensitive functionalities are present. Methyl and benzyl esters, and the isopropylidene group were partially deprotected at 50°C under the reaction conditions.
23. Typical procedure for BOC deprotection: To a solution of 2-tert-butoxycarbonylamino-succinic acid 1-benzyl ester (1.0 g, 2.73 mmol) in tetrahydrofuran (1 mL) at room temperature (entry 1, Table 1), was added aqueous phosphoric acid (85 wt%, purchased from Aldrich Chemical Co.) (2.81 mL, 41 mmol) dropwise. The mixture was stirred for 4 h, and HPLC assay showed reaction completion. 5 mL of water was added, and the mixture was cooled to 0°C. 50 wt% NaOH solution was added slowly (Caution: exothermic) to adjust to the pH to ∼8. The mixture was then extracted with ethyl acetate (2×20 mL). The combined ethyl acetate phase was dried over magnesium sulfate, concentrated in vacuo to give the desired product as a white solid (0.57 g, 94%). The product showed 98.7% HPLC purity (by area%). It co-eluted with an authentic sample by HPLC.
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29. The isolation was simplified by direct dilution with water, followed by extractive workup and isolation using ethyl acetate.