Sodium Borohydride Reduction and Selective Transesterification of β-Keto Esters in a One-pot Reaction under Mild Conditions

Abstract

An efficient and simple one-pot method of preparing β-hydroxy esters by sodium borohydride reduction cum selective transesterification of β-keto esters under mild conditions is described.

Key words

transesterification - β-keto esters - β-hydroxy esters - sodium borohydride - one-pot reaction

References

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16

Experimental:
Typical Reduction cum Transesterifcation Reaction: Ethyl benzoylacetate, 1 mL (5.78 equiv) in methanol, 15mL was treated with sodium borohydride, 110 mg (2.89 equiv) at 0 °C to r.t. The reaction was carried out for 18 h. Routine workup gave a reaction mixture which was purified by column chromatography and characterized by ¹H NMR.

17

Large excess of alcohol improves the yield of the reaction. The isolated yield in these reactions is limited because of two reasons: a) during work up of the reaction a loss of
10-15% was observed due to the formation of the corresponding hydroxy acid and b) separation by column chromatography of two similar compounds (two β-hydroxy esters), is challenging and leads to a loss of 10-12%.

18

The spectral data (for the product of entry 15): ¹H NMR (CDCl₃): δ = 2.50 (s, 1 H), 2.70 (double dd, 2 H), 3.30 (br s, 1 H), 4.67 (s, 2 H), 5.10 (m, 1 H), 7.33 (s, 5 H). ¹³C NMR:
δ = 171.27 (C1), 142.48 (C4, arom.), 125.60, 127.30, 129.30 (arom.), 77.70 (C3), 76.60 (C2′), 70.20 (C3′), 50.70 (C1′), 43.20 (C2).

19

During the course of above experiment an aliquot of (1mL) was always taken at equal intervals of time (15 min), neutralized and extracted. Each of them was monitored by ¹H NMR.

20

Sodium borohydride catalyzed borohydride reducing systems, Thiokol/ventron division, 150 Andover street, Danvers, Massachusetts, 01923, U.S.A., [phone], 3.

21

Methyl 3-hydroxy butyrate was treated with sodium ethoxide in presence of large excess of dry ethanol and the reaction was allowed to run for more than 2 h.