Process for producing optically active tetrahydrofuran-2-carboxylic acid
A technique for producing tetrahydrofuran, applied in organic chemistry methods, chemical instruments and methods, organic chemistry, etc., can solve the problems of cumbersome purification process, residual, expensive, etc., and achieve the effect of high optical purity and high productivity
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[0052] The invention is illustrated by the following examples.
[0053] The chemical purity and optical purity in the examples were measured by the methods shown below.
[0054]
[0055] High performance liquid chromatography (HPLC) analysis conditions
[0056] Column: Inertsil ODS-34.6mmφ×150mm, 0.25μm (GL Sciences)
[0057] Mobile phase: A liquid: 20mM phosphate buffer (pH2.1), B liquid: acetonitrile
[0058] Gradient: A / B=80 / 20 (3 minutes) → 25 minutes → 50 / 50 (10 minutes) → 2 minutes → 80 / 20 (5 minutes)
[0059] Flow rate: 1mL / min
[0060] Column temperature: 40°C
[0061] Detector: UV (230nm)
[0062] Retention time: 3.1 minutes (tetrahydrofuran-2-carboxylic acid)
[0063]
[0064] High performance liquid chromatography (HPLC) analysis conditions
[0065] Column: SUMICHIRAL OA-60004.6mmφ×250mm, 5μm (Sumichiral Analytical Center)
[0066] Mobile phase: 2mM copper (II) sulfate aqueous solution / acetonitrile=90 / 10 (v / v)
[0067] Flow rate: 1.0ml / min
[0068] Col...
reference example 1
[0072] Reference Example 1 (R) - Production of tetrahydrofuran-2-carboxylic acid benzylamine salt
[0073] Add 200 g (1.72 moles, 96.2% e.e. (R)) of a mixture of (R)- and (S)-tetrahydrofuran-2-carboxylic acid, 2-propanol to a 2L four-necked flask equipped with a thermometer, condenser and stirrer. 700g, heated up to 65°C. 203 g (1.90 moles) of benzylamine was added dropwise at 60-70°C, and after complete dissolution, the temperature was lowered to 65°C, and then seed crystals were added, and aged at around 65°C for 1 hour. Then, it was slowly cooled to 20° C., aged at around 20° C. for 1 hour, and the precipitated crystals were filtered and dried under reduced pressure to obtain 337.2 g of (R)-tetrahydrofuran-2-carboxylic acid·benzylamine salt. The optical purity of this salt was 99.5%e.e., and the yield of the R-isomer in the obtained salt was 89.6% with respect to the R-isomer of tetrahydrofuran-2-carboxylic acid charged.
[0074] 1 H-NMR (DMSO-d 6 ,400MHz) δppm: 7.43-7....
Embodiment 1
[0078] (first process)
[0079] Add 337.2 g of (R)-tetrahydrofuran-2-carboxylic acid benzylamine salt obtained in Reference Example 1, 272.6 g of water, and 192.5 g of 32% sodium hydroxide aqueous solution to a 2 L four-necked flask equipped with a thermometer, a condenser, and a stirrer. g (1.54 moles) to allow complete dissolution. Next, 175 g of toluene was added, and benzylamine was extracted and removed to the toluene layer side. After confirming that the benzylamine was removed, 175 g of tetrahydrofuran was added, and after standing still, the tetrahydrofuran layer was removed by liquid separation and washed to obtain 688.8 g of an aqueous layer.
[0080] (second process)
[0081] Add 688.8 g of the washed water layer obtained in the first step to a 2L four-neck flask equipped with a thermometer, condenser and stirrer, add 75.5 g of 98% sulfuric acid dropwise at 35°C to 45°C, Cake at ℃ for 1 hour, then separate the liquids. Furthermore, 87.7 g of tetrahydrofuran was ...
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