Chemical Properties
Light yellowish liquid
Uses
O-tert-Butylthreonine tert-Butyl Ester, can be used in the synthesis of various chemical compounds having therapeutic activity, such as N-[[[(1S)-1-[3-(2-Pyrazinyl)-1,2,4-oxadiazol-5-yl]-3-butyn-1-yl]amino]carbonyl]-L-threonine (P842605), used as immune modeulators.
Synthesis
(1) Add 250 μL of bis-L-threonine and 1750 g of ethylene glycol dimethyl ether to a 5000 mL three-neck flask. After cooling the flask to -10 to -5 °C, 1000 g of trifluoromethanesulfonic acid was slowly added dropwise at -5 to 5 °C. (2) To the reaction mixture was added 1250 g of isobutene at -15 to -10 °C. The reaction temperature was controlled at -15 to -10°C for 48 hours. (3) Upon completion of the reaction, 2500 g of water was added to the reaction mixture at -5 to 5 °C, followed by 1500 g of 20-25% ammonia to adjust the pH to 7.5-8.0. The aqueous phase was extracted with 1000 mL of ether in two portions and the organic phases were combined. The organic phase was washed three times with 250 mL of water and dried by adding 50 g of anhydrous sodium sulfate. Concentrate to dryness under reduced pressure at 50 °C to obtain 360 g of crude product with 95% purity (GC) and 70.44% yield. Purification of crude product: 360 g of crude product was dissolved in 1500 g of hexane, 5 g of activated carbon was added, decolorized at 25-35 °C for 1 h, filtered, and the filter cake was washed with 150 g of hexane. To the filtrate was added 93.0 g of glacial acetic acid (calculated amount: 360 x 95% ÷ 231.33 x 1.05 x 60 = 88.0 g), stirred at 15-25 °C for 2 h, and then slowly cooled to 0-5 °C and kept for 2 h. The filtrate was then dried for 1 h and then dried for 2 h. The crystals were separated by centrifugation and rinsed with a small amount of hexane. The wet crystals were dried under vacuum at 45 °C to give 415 g of product with 99.40% purity and 67.87% yield. Dissolve 415 g of the acetate product in 800 g of water, add 500 mL of hexane and stir to dissolve, add about 120 g of sodium bicarbonate to adjust the pH to 7.5-8.0. Separate the phases, and the aqueous phase was extracted twice consecutively with 500 mL of hexane. The organic phases were combined, washed three times with 300 mL of water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 326.20 g of liquid product with 99.69% purity and 67.20% yield.
References
[1] Patent: CN106478439, 2017, A. Location in patent: Paragraph 0028; 0029; 0030; 0031; 0032; 0033; 0034-0047
[2] Patent: WO2005/23756, 2005, A1. Location in patent: Page/Page column 5
