Isopropyl Acetate → Di-tert-butyl (chloromethyl) phosphate

温度

35 °C

To a mixture of potassium ditert-butyl phosphate (261 kg, 1.00 mol eq), tetra-n-butylammonium hydrogensulphate (18.5 kg, 0.05 mol eq) and sodium hydrogencarbonate (400 kg, 4.50 mol eq) in water (1150 kg) is added isopropyl acetate (1275 kg). The mixture is warmed to about 35° C. and then to this is added chloromethylchlorosulphate (313 kg, 1.80 mol eq) over about 4 hours. The mixture is further stirred for about 45 minutes, cooled to about 25° C. and then the layers separated. The organic phase is cooled to about 10° C. and washed twice with 2% w/v aqueous potassium hydrogencarbonate solution (2×800 kg) and then with a mixed 2% w/v potassium hydrogencarbonate and 20% w/v potassium hydrogencarbonate aqueous solution (640 kg). The resulting organic solution is then distilled at <100 mbar to half volume, maintaining the temperature below 45° C. The resulting mixture is filtered, washing the filter with isopropyl acetate (115 kg), to give the title compound as a solution, with typical solution strength of about 25% w/v and yield of about 90%. This solution is then used directly in Example 1, Step C.

1. temperaturecooled to about 25° C.
2. customthe layers separated
3. temperatureThe organic phase is cooled to about 10° C.
4. washwashed twice with 2% w/v aqueous potassium hydrogencarbonate solution (2×800 kg)
5. distillationThe resulting organic solution is then distilled at <100 mbar to half volume
6. temperaturemaintaining the temperature below 45° C
7. filtrationThe resulting mixture is filtered
8. washwashing the
9. filtrationfilter with isopropyl acetate (115 kg)

ORDレコード

ord-c96ff090b8de4b54afaedfbba6baad46

出典データセット

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09388203B2