Synthesis
Tetrahydrofuran (THF) was dehydrated through 4Å molecular sieves overnight and set aside. Under nitrogen protection, 2.2 kg of dehydrated THF was added to a 5 L four-necked flask and cooled to below 10 °C. 50 g of lithium aluminum hydride was slowly added, followed by dropwise addition of 250 g of ethyl 3,3-diethoxypropionate, controlling the internal temperature not to exceed 10 °C. After the dropwise addition was completed, the temperature was raised to 20°C and the reaction was carried out for 1 hour. After completion of the reaction, 420 g of distilled water was added and stirred for 2 h. The filtrate was filtered through No. 2 filter paper and the cake was washed with 1.1 kg of THF. The filtrate was concentrated at 40 °C to give 213 g of crude 3,3-diethoxy-1-propanol (abbreviated as 33DEP). 200g of crude 33DEP was taken in a 5L four-necked flask, 1kg of hexane was added and stirred for 1 hour (Step A). Add 1kg of 0.1M phosphate buffer (pH 7.5), stir for 20 minutes and transfer to a 5L separatory funnel and leave to stratify. After separating the aqueous layer, the hexane layer was returned to the flask and the aqueous layer was recovered by repeating the addition of 1 kg of 0.1 M phosphate buffer (pH 7.5), stirring for 20 minutes, and again transferring to a partitioning funnel for stationary partitioning (Step B). The combined aqueous layer was transferred back to a 5L four-necked flask, 2kg of chloroform was added, stirred for 30 minutes, transferred to a 5L partition funnel and left to stratify for 15 minutes. The chloroform layer was recovered and the aqueous layer was repeated once with 2 kg chloroform extraction and the chloroform layers were combined (Step C). The chloroform layer was concentrated at 40°C and residual solvent was removed by nitrogen bubbling. 20g of 4Å molecular sieve was added and filtered after stirring for 5 h to give 188 g of 33DEP. 150 g of 33DEP was taken in a 300 mL four neck flask and subjected to reduced pressure distillation. The first fraction was collected at 0.4 kPa, bath temperature of 38°C, internal temperature of 36°C, and temperature at the top of the tower of 33°C. Subsequently, the bath temperature was gradually increased, and the main fraction was collected at 0.2 kPa, bath temperature of 58 °C, internal temperature of 55 °C, and temperature of the top of the tower of 54 °C, and the temperature of the top of the tower was controlled not to exceed 60 °C, and finally 138 g of the main fraction was obtained (Step D). The main fraction was analyzed by GC and the results are shown in Table 1.
References
[1] Patent: US2012/277477, 2012, A1. Location in patent: Page/Page column 5
[2] Acta Chemica Scandinavica (1947-1973), 1973, vol. 27, p. 239 - 250
[3] Patent: US4634773, 1987, A
