Sodium Carbonate → (3S,7aR)-7a-cyclopropyl-3-phenyl-2,3-dihydropyrrolo[2,1-b]oxazol-5(7aH)-one

To potassium hydride (35 weight % in oil, washed with heptane (×3), 3.01 g, 26.3 mmol), in THF (20 mL) was added a solution of (3S,7aS)-7a-cyclopropyl-3-phenyltetrahydropyrrolo[2,1-b]oxazol-5(6H)-one (preparation #23) (2.56 g, 10.5 mmol) in THF (20 mL) dropwise via an addition funnel. A solution of methyl benzenesulfinate (1.97 g, 12.6 mmol) in THF (20 mL) was then added dropwise via an addition funnel. The reaction mixture was stirred at ambient temperature for about 16 hours. The reaction was quenched by the addition of water (4.2 mL). The mixture was concentrated and the residue was partitioned between 0.5 M H3PO4 (100 mL) and DCM (200 mL). The layers were separated and the aqueous layer was extracted with DCM (3×100 mL). The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated to yield a light brown solid. Toluene (83 mL) was added followed by solid Na2CO3 (10.35 g). The reaction mixture was refluxed for about 16 hours and then filtered and concentrated in vacuo. The residue was purified on a Biotage silica gel column eluting with heptane/EtOAc (4:1). A second purification on silica gel eluting DCM/EtOAc (1:0 to 4:1) afforded (3S,7aR)-7a-cyclopropyl-3-phenyl-2,3-dihydropyrrolo[2,1-b]oxazol-5(7aH)-one (1.82 g, 7.57 mmol). 1H NMR (CDCl3-d) δ 7.34 (m, 4H), 7.28 (m, 1H), 7.11 (d, 1H), 6.08 (d, 1H), 5.06 (t, 1H), 4.69 (t, 1H), 4.43 (dd, 1H), 1.14 (m, 1H), 0.45 (m, 2H), 0.32 (m, 1H), 0.21 (m, 1H).

1. customThe reaction was quenched by the addition of water (4.2 mL)
2. concentrationThe mixture was concentrated
3. customthe residue was partitioned between 0.5 M H3PO4 (100 mL) and DCM (200 mL)
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with DCM (3×100 mL)
6. washThe combined organic extracts were washed with brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto yield a light brown solid
11. temperatureThe reaction mixture was refluxed for about 16 hours
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customThe residue was purified on a Biotage silica gel column
15. washeluting with heptane/EtOAc (4:1)
16. customA second purification on silica gel
17. washeluting DCM/EtOAc (1:0 to 4:1)

ORD record

ord-9ecae67afbdf44a3b692c541dfb92157

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08754107B2