Triethylamine → 2,5-Anhydro-3,4-dideoxy-1,6-bis-o-(methylsulfonyl)hexitol

関与物質

反応条件

反応手順

Methanesulphonyl chloride (307.8 g, 2.7 mol) is added dropwise to a solution of tetrahydrofuran-2,5-dimethanol (118.8 g, 900 mmol) and of triethylamine (454.5 g, 4500 mmol) in 1.54 L of dichloromethane at 0° C. The reaction medium is maintained at 0° C. for 1 hour, ice-cold water is then added and the organic phase is separated out and washed with 500 mL of dilute (1 M) hydrochloric acid solution. The organic phase is separated out and then washed with 500 mL of saturated aqueous NaHCO3 solution. The organic phase is finally separated out and concentrated to give 236.7 g of (tetrahydrofuran-2,5-diyl)bis(methylene) dimethanesulphonate in the form of a brown oil in a purity equal to 96% (determined by LCMS). Reaction yield: 91.0%. A solution of (tetrahydrofuran-2,5-diyl)bis(methylene) dimethanesulphonate (236.7 g, 821.7 mmol) and NaN3 (270.0 g, 4.1094 mol) in DMSO (1.350 L) is heated at 95° C. and stirred overnight. The reaction medium is added to ice-cold water and extracted with 3 times 700 mL of ethyl acetate. The extracts (phase containing ethyl acetate) are successively washed with water, saturated aqueous NaHCO3 solution and dried overnight on MgSO4 and then filtered to remove the MgSO4. The phase containing the ethyl acetate is concentrated to give 166.5 g of 2,5-bis(azidomethyl)tetrahydrofuran in the form of a brown oil. A mixture of 2,5-bis(azidomethyl)tetrahydrofuran (166.5 g) and of Pd-C (10%, 10.8 g) in methanol (2.7 L) is stirred overnight at room temperature under 1 atm of H2. The reaction medium is filtered and the filtrate is concentrated under vacuum to give 90.0 g of 2,5-bis(aminomethyl)tetrahydrofuran in the form of a yellow oil. The total yield for the 3 successive reactions is 75%. The process for synthesizing 2,5-bis(aminomethyl)tetrahydrofuran gives a 90/10 mixture of the cis/trans isomers according to 13C NMR analysis in deuterated methanol.

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