Sodium Hydroxide → (R)-3,3-dimethylbutane-1,2,4-triol

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Adapting a procedure or a variation thereof according to Blakemore et al., J. Org. Chem. 2005, 70, 5449-5460; Mandel et al., Org. Lett. 2004, 6(26), 4801-4803; Lavallée et al., Tetrahedron Lett. 1986, 27, 679-682; Shiina et al., Bull. Chem. Soc. Jpn. 2001, 74, 113-122; Ito et al., Synthesis 1993, 137-140; Callant et al., Tetrahedron: Asymmetry 1993, 4(2), 185-188; Dolle et al., J. Am. Chem. Soc. 1985, 107, 1691-1694; and Matsuo et al., Tetrahedron Lett. 1976, 17(23), 1979-1982, a dry 1,000 mL three-necked flask equipped with a magnetic stirring bar, addition funnel, and reflux condenser topped with rubber septa was charged under a nitrogen atmosphere with 7.8 g (60.0 mmol) of commercially available D-pantolactone. The material was dissolved in 100 mL of anhydrous tetrahydrofuran (THF) and the solution cooled to ca. 0° C. (ice bath). Sixty-five (65) mL (38.5 mmol) of a one molar (1.0 M) solution of lithium aluminum hydride (LAH) in THF was added dropwise and the reaction mixture stirred overnight with gradual warming to room temperature. (Note: To ensure complete global reduction of the lactone several authors recommend heating the reaction mixture to reflux for ca. two hours after the overnight reaction to complete the reduction.) The reaction mixture was again cooled to ca. 0° C. (ice bath) and 4.23 mL of water, 8.46 mL of an aqueous solution of sodium hydroxide (10 wt-%), and 4.23 mL of water were carefully added (Note: Initially, there is a vigorous evolution of hydrogen gas.) and the resulting colorless precipitate was filtered off The filter residue was washed with dichloromethane (DCM) and the combined filtrates were dried over anhydrous magnesium sulfate (MgSO4). After filtration and evaporation of the solvents under reduced pressure using a rotary evaporator, 6.6 g (82% yield) of the title compound (6) was obtained as a slightly yellow, viscous liquid that was of sufficient purity to be used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ=0.768 (s, 3H), 0.777 (s, 3H), 3.15 (d, J=10.4 Hz, 1H), 3.21 (d, J=10.0 Hz, 1H), 3.22-32 (m, 2H), 3.44-3.52 (m, 1H), 4.20-4.40 (br. m, 3H) ppm. MS (ESI) m/z: 135.03 (M+H)+, 132.89 (M−H)−. The analytical data for the compound was consistent with the proposed structure and the data given in the literature.

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