Acetic Acid → (7R,7aR)-2-chloro-4-(7-hydroxy-7a-methyl-3-oxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile

To a solution of (7R,7aR)-4-[7-(tert-Butyldimethylsilanyloxy)-7a-methyl-3-oxotetrahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile (58E) (17 mg, 0.04 mmol) in THF (2 mL) was added acetic acid (100 □L) and a 1 M solution of TBAF in THF (122 □L, 0.12 mmol). After stirring at rt for 11 h, additional TBAF solution was added (100 □L), and after stirring for another 6 h, 200 □L TBAF solution was added. The reaction was stirred overnight, then 100 □L TBAF was added and the reaction stirred an additional 1.5 h. The reaction was then quenched with saturated aqueous NH4Cl and extracted with EtOAC. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated under reduced pressure. The resulting residue was purified via preparative HPLC (Luna C-18, 100×21.2 mm, eluting with 40-100% solvent B (A=90% H2O—10% MeOH—0.1% TFA and B=10% H2O—90% MeOH—0.1% TFA) over 10 min; Flow rate at 20 mL/min; UV detection at 220 nm) to provide the title compound (11 mg). LC/MS m/z 306 [M+H]+.

1. stirringafter stirring for another 6 h
2. stirringThe reaction was stirred overnight
3. stirringthe reaction stirred an additional 1.5 h
4. customThe reaction was then quenched with saturated aqueous NH4Cl
5. extractionextracted with EtOAC
6. washThe organic layer was washed with brine
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe resulting residue was purified via preparative HPLC (Luna C-18, 100×21.2 mm
11. washeluting with 40-100% solvent B (A=90% H2O—10% MeOH—0.1% TFA and B=10% H2O—90% MeOH—0.1% TFA) over 10 min

ORD record

ord-82d3af4ae1ed44319e62354fa86592ad

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07405234B2