(S)-(+)-3-Hydroxytetrahydrofuran

Description

(S)-(+)-3-Hydroxytetrahydrofuran (3-OH THF) is a colorless liquid with a normal boiling point of 179 °C and boiling at 88-89 °C at 17 mmHg, with density (1.087 g/cm3 at 19 °C). 3-OH THF is a useful pharmaceutical intermediate. The chiral (absolute configuration S) version of this compound is an intermediate to launched retroviral drugs.

Chemical properties

Colourless Liquid

The Uses of (S)-(+)-3-Hydroxytetrahydrofuran

(S)-(+)-3-Hydroxytetrahydrofuran is a useful reagent for the preparation of pyrazolo triazin ylamine derivatives as adenosine receptor antagonists.

The Uses of (S)-(+)-3-Hydroxytetrahydrofuran

(S)-(+)-3-Hydroxytetrahydrofuran is an intermediate to the AIDS drugs amprenavir and fosamprenavir. Additionally, it has been an intermediate to developmental drug substances, such as chemotherapy agents.

Synthesis

(S)-(+)-3-Hydroxytetrahydrofuran was prepared from the reaction of (S)-1,2,4-butanetriol under hydrochloric acid modified montmorillonite catalyst. The steps were as follows：To the heatable reactor (with stirring device), 100g (S)-1,2,4-butanetriol, 200mL toluene, 15g hydrochloric acid modified montmorillonite catalyst prepared in were added successively. The reaction was stopped after 4 h at 110°C. After the reaction is finished, it is naturally cooled to room temperature, and the obtained material is filtered to recover the catalyst. After collecting the filtrate, the remaining solvent and by-product water in the filtrate are distilled off to obtain (S)-3-hydroxytetrahydrofuran crude product. Quantitative analysis was carried out by gas chromatography, and the yield was 96.8%. Finally, the (S)-3-hydroxytetrahydrofuran was obtained by rectification and purification.

Preperation

The preparation methods of (S)-(+)-3-Hydroxytetrahydrofuran include chiral substrate synthesis, chiral catalyst asymmetric synthesis, and enzyme-catalyzed asymmetric synthesis.
Using dimethyl L-malate as raw material, dimethyl (s)-2-tert-butyloxybutyrate was first protected by isobutene and then reduced to (s)-2-tert-butyloxybutanol with cheap NaBH4 as reductant. Finally, under the catalysis of p-toluene sulfonic acid, the product (S)-(+)-3-Hydroxytetrahydrofuran was obtained through 2-position deprotection, dehydration, and cyclization, with a yield of 65%.