Methyl iodide → HCID 11378527, compound

To a solution of lithium diisopropylamide, prepared by adding nBuLi (2.5 M sol. in hexanes, 1.36 mL, 3.39 mmol) to diisopropylamine (477 μL, 3.39 mmol) in THF (15 mL) at 0° C., was added a pre-cooled solution of known (3aS,6aR)-3,3a,6,6a-tetrahydro-2H-cyclopenta[b]furan-2-one (+)-115 (350 mg, 2.82 mmol) in THF (5 mL+3 mL rinse) at −78° C., dropwise. The reaction mixture was stirred at this temperature for 30 min, then methyl iodide (352 μL, 5.65 mmol) was added dropwise and the reaction mixture was stirred at −78° C. for 6 h. The reaction mixture was quenched with 2 M aqueous HCl. The aqueous phase was extracted with Et2O (×3). The combined organic layer was dried (Na2SO4), filtered, and concentrated under vacuum. The residue was purified by column chromatography on silica gel using hexanes/Et2O (5:1) to yield lactone 116 (369 mg, 95%) as a brown oil. TLC: Rf=0.54 (hexanes/EtOAc=2:1); [α]D20+54.2 (c 1.0, CHCl3); 1H NMR (CDCl3, 400 MHz) δ 5.74 (m, 1H), 5.59 (m, 1H), 5.12 (t, J=5.6 Hz, 1H), 3.13 (dd, J=3.8, 1.8 Hz, 1H), 2.65 (m, 2H), 2.52 (q, J=7.6 Hz, 1H), 1.33 (d, J=7.6 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 180.0, 130.9, 129.4, 81.3, 53.8, 39.9, 39.2, 17.4.

1. stirringthe reaction mixture was stirred at −78° C. for 6 h
2. customThe reaction mixture was quenched with 2 M aqueous HCl
3. extractionThe aqueous phase was extracted with Et2O (×3)
4. dry with materialThe combined organic layer was dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated under vacuum
7. customThe residue was purified by column chromatography on silica gel

ORD record

ord-60a30412211d46de8dde99a94c29e346

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309213B2