Hydrochloric Acid → rac-Methyl 5,5,6,6,6-pentafluoronorleucinate hydrochloride

Temperatur

-40 °C

Under argon, 132 g (521.0 mmol) of methyl N-(diphenylmethylene)glycinate [described in: WO2010/123792 A1, 2010, 11-13; additionally: commercially available] were initially charged in 1000 ml of THF (anhydrous) and cooled to −40° C. 625.2 ml (625.2 mmol) of bis(trimethylsilyl)lithium amide (1 M in THF) were added dropwise over 30 min. After 10 min, the cooling bath was replaced by a water/ice bath, and the internal temperature was allowed to increase to 0° C. over a period of 35 min. At 0° C., 192.86 g (651.25 mmol) of 3,3,4,4,4-pentafluorobutyl trifluoromethanesulphonate from Example 132A, dissolved in 400 ml of THF, were added dropwise to the reaction solution. After 10 min, the cooling bath was removed and the mixture was stirred at RT for 3 days. The reaction mixture was then cooled to 0° C., and 410 ml (1.33 mol) of 3 N hydrochloric acid were added dropwise. The cooling bath was removed and the reaction solution was stirred at RT for 2 hours. The mixture was then concentrated. This gave 141.5 g of the target compound as a crude mixture which was used without any further purification for the next step.

1. customthe cooling bath was replaced by a water/ice bath
2. temperatureto increase to 0° C. over a period of 35 min
3. additionwere added dropwise to the reaction solution
4. waitAfter 10 min
5. customthe cooling bath was removed
6. temperatureThe reaction mixture was then cooled to 0° C.
7. customThe cooling bath was removed
8. stirringthe reaction solution was stirred at RT for 2 hours
9. concentrationThe mixture was then concentrated
10. customThis gave 141.5 g of the target compound as a crude mixture which was used without any further purification for the next step

ORD-Eintrag

ord-27566bf1389942c99b8d8b8bf0fc3f4b

Quelldatensatz

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08946215B2