反应详情

温度

-5 °C

Following a procedure reported by Hoffmann, M., Synthesis (1986), 557A, a solution of (R)-1-(benzyloxycarbonyl)amino-2-methylpropylphosphonic acid (691.0 mg, 2.41 mmol) in 8 mL of DMF was cooled to −20° C. using a dry ice/methanol bath. To this solution was added thionyl chloride (0.21 mL, 2.88 mmol) and stirred at −5° C. for 25 minutes. Racemic 2-hydroxy-2-(3-(t-butoxycarbonylamino)phenyl)ethanoic acid methyl ester (683.4 mg, 2.43 mmol) was added as a solution in 2 mL of DMF and the reaction was allowed to warm to ambient temperature. After stirring for 4 days (total reaction time 87 hrs), the reaction had almost gone to completion (95%). To this reaction mixture 5 mL of saturated NaHCO3 was added. The solution was washed with ether (2×), acidified to pH 2 with concentrated HCl, and extracted with ethyl acetate (3×). The combined ethyl acetate extracts were dried over MgSO4, filtered, and concentrated in vacuo to give a mixture of product and starting material. Purification via SiO2 gel flash column chromatography (CH2Cl2, then methanol) provided 1.1966 g (90%) of 2-(3-(t-butoxycarbonylamino)phenyl)-2-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(hydroxy)phosphinoyloxy)ethanoic acid methyl ester; as a mixture of diastereomers.

1. temperatureto warm to ambient temperature
2. stirringAfter stirring for 4 days (total reaction time 87 hrs)
3. washThe solution was washed with ether (2×)
4. extractionextracted with ethyl acetate (3×)
5. dry with materialThe combined ethyl acetate extracts were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto give
9. additiona mixture of product
10. customPurification via SiO2 gel flash column chromatography (CH2Cl2