Trifluoroacetic anhydride → HCID 11118371, compound

Temperature

20 °C

Trifluoroacetic anhydride (17.6 g) was added dropwise to a stirred solution of crude product of Step 3 in tetrahydrofuran (220 ml) with water bath cooling to 20° C. After 2 hours the mixture was left to stand for 20 hours. A solution of sodium hydrogen carbonate (14.1 g) in water (220 ml) was added during 5 minutes with stirring and cooling to 20° C. After 30 minutes the mixture was refluxed for 41/2 hours, cooled to 25° C., extracted with dichloromethane (3×300 ml), the extract dried over magnesium sulphate, filtered and concentrated under reduced pressure to give a brown oil (21.4 g). The brown oil (20.09 g) was dissolved in 1,4-dioxane (500mi) and hydrogen chloride gas bubbled in for 31/4 hours, with stirring, at 23° C. The mixture was left in a stoppered flask for 20 hours, concentrated under reduced pressure, dissolved in dichloromethane (400 ml), neutralised with a minimum of saturated aqueous sodium hydrogen carbonate, dried over magnesium sulphate, filtered and concentrated under reduced pressure to a brown oil (21.9 g). The oil was subjected to column chromatography on silica gel, gradient eluting with dichloromethanet-butyl methylether mixtures to give the crude product as a yellow gum (4.7 g). The gum was crystallised from hexane solution to give a yellow solid. 1H NMR (CDCl3): δ 4.43(1 H,bs); 5.49(1 H,s); 5.68(2 H,m); 7.49-7.8(4 H,m).

1. waitto stand for 20 hours
2. temperaturecooling to 20° C
3. temperatureAfter 30 minutes the mixture was refluxed for 41/2 hours
4. temperaturecooled to 25° C.
5. extractionextracted with dichloromethane (3×300 ml)
6. dry with materialthe extract dried over magnesium sulphate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure

ORD record

ord-b6585ff852e649d3a91aa37e028caa54

Source dataset

uspto-grants-1997_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05688962