Formic Acid → HCID 58011472, compound

Temperature

40 °C

The (3R,6R,7aS)-6-(3-chloropropyl)-3-phenyl-dihydropyrrolo[1,2-c]oxazol-5(1H,3H,6H)-one (13.6 g, 47.9 mmol, 1.0 equiv) was dissolved in a mixture of THF (100 mL):formic acid (85%, 62.5 mL):H2O (31 mL) and the solution heated to 40° C. for 3.5 h. After this time the animal was consumed and the desired alcohol was contaminated with varying amounts of the formate ester. The solution was evaporated using a rotory evaporator, maintaining the bath temperature below 25° C. A solution of 1.9 M LiOH was added to the residue till a pH>12 was achieved and the mixture stirred for 20 min. After this time no formate ester was observed. EtOAc (250 mL was added and the mixture transferred to a separatory funnel. The layers were separated and the aqueous layer was extracted with 4×50 mL of EtOAc. The combined extracts were dried over Na2SO4, filtered and evaporated. Hexanes (˜200 mL) were added to the residue and the biphasic mixture heated to ˜40° C. The hexanes were decanted off and the procedure repeated twice. The resulting syrup was placed on a vacuum line where it solidified to yield (3R,5S)-3-(3-chloropropyl)-5-(hydroxymethyl)pyrrolidin-2-one as an off-white solid (7.51 g 82% yield). An additional 0.80 g of material may be obtained by saturating the above aqueous solution with NaCl and extracting with 4×50 mL of CH2Cl2.

1. customAfter this time the animal was consumed
2. customThe solution was evaporated
3. customa rotory evaporator
4. temperaturemaintaining the bath temperature below 25° C
5. additionA solution of 1.9 M LiOH was added to the residue till a pH>12
6. additionEtOAc (250 mL was added
7. customthe mixture transferred to a separatory funnel
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with 4×50 mL of EtOAc
10. dry with materialThe combined extracts were dried over Na2SO4
11. filtrationfiltered
12. customevaporated
13. additionHexanes (˜200 mL) were added to the residue
14. customThe hexanes were decanted off

ORD record

ord-c0f4bcfba01f4b9d858145c3b95b3b48

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08198453B2