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Synlett 2010(14): 2141-2145  
DOI: 10.1055/s-0030-1258491
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Mild and Catalytic Transesterification Reaction Using K2HPO4 for the Synthesis of Methyl Esters

Tetsuro Shinada*, Makoto Hamada, Kota Miyoshi, Masato Higashino, Taiki Umezawa, Yasufumi Ohfune*
Graduate School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi, Osaka 558-8585, Japan
Fax: +81(6)66053153; e-Mail: ohfune@sci.osaka-cu.ac.jp; e-Mail: shinada@sci.osaka-cu.ac.jp;
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Publikationsverlauf

Received 5 May 2010
Publikationsdatum:
09. Juli 2010 (online)

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Abstract

K2HPO4 is an efficient catalyst for the transesterification reaction to produce methyl esters. Various functional groups are compatible under the mild reaction conditions.

Key words

transesterification - K2HPO4 - methyl ester - catalyst

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  • 9b

    A mixture of 38 (130 mg, 0.33 mmol) in AcOH-THF-H2O (5:1:1, 0.7 mL) was stirred for 12 h and concentrated under reduced pressure. The remaining AcOH and H2O were removed as an azeotropic mixture of toluene. The crude 39 was subjected to the next step without purification. Analytical data of 39: ¹H NMR (400 MHz, CDCl3): δ = 7.76 (d, J = 7.3 Hz, 2 H), 7.60 (d, J = 7.3 Hz, 2 H), 7.40 (t, J = 7.3 Hz, 2 H), 7.39 (t, J = 7.3 Hz, 2 H), 5.45 (br s, 1 H), 4.41 (d, J = 7.1 Hz, 2 H), 4.21-4.25 (m, 3 H), 4.01 (br s, 1 H), 3.55 (br s, 4 H), 0.85 (s, 3 H).

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    To a solution of 39 in MeOH (3.5 mL) was added K2HPO4 (0.11 mmol). The mixture was heated to reflux for 1 h and concentrated under reduced pressure. The crude mixture was diluted with EtOAc-hexane (1:1, 10 mL) and filtered through a thin silica gel pad. The filtrate was concentrated under reduced pressure to give 40 in 94% yield. The analytical data were identical to the authentic data.¹0

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8

Typical Synthetic Procedure: To a solution of the N-Cbz-threonine ethyl ester (7; 1 mmol) in MeOH (10 mL) was added K2HPO4 (0.1 equiv). The mixture was heated at reflux for 1 h and concentrated under reduced pressure. The crude material was then dissolved in EtOAc-hexane (1:1, 10 mL). The mixture was filtered through a thin silica gel pad. The filtrate was concentrated under reduced pressure to give the N-Cbz-threonine methyl ester(8) in 92% yield.

11

The role of K2HPO4 in the mild transesterification reaction has been unclear. In our experiments using various inorganic salts, the reaction rate and product yield were varied and not necessarily dependent on the cationic or anionic nature of inorganic salts.