(3aR,6aR)-2,2-dimethyl-2H,3aH,4H,6aH-cyclopenta(d)(1,3)dioxol-4-one → (3aR,6S,6aR)-2,2,6-trimethyl-3a,5,6,6a-tetrahydrocyclopenta[d][1,3]dioxol-4-one

Temperature

-40 °C

Copper(I) iodide (3.7 g, 19.5 mmol, 5 equiv) was suspended in Et2O (35 mL) and cooled to −40° C. Methyllithium (20.2 mL, 32.3 mmol, 8.3 equiv, 1.6M in THF) was added dropwise over 45 minutes. The mixture was warmed to 0° C. and (3aR,6aR)-2,2-dimethyl-3aH-cyclopenta[d][1,3]dioxol-4(6aH)-one (5-1) (600 mg, 3.9 mmol, 1 equiv) in 1:1 THF/Et2O (20 mL) was added dropwise over 10 minutes. The resulting mixture was stirred warming to ambient temperature over 1 hour. The mixture was then cooled to 0° C., quenched carefully with 25 mL of 15% acetic acid and extracted with EtOAc (3×40 mL). The combined organics were washed with NH4Cl (50 mL), dilute NH4OH (2×50 mL) and water (50 mL), dried over MgSO4, filtered and concentrated to afford (3aR,6S,6aR)-2,2,6-trimethyldihydro-3aH-cyclopenta[d][1,3]dioxol-4(5H)-one (6-1) as a light yellow oil. 1H NMR (500 MHz, CDCl3): δ 4.50 (d, J=5.5 Hz, 1H); 4.23 (d, J=5.0 Hz, 1H); 2.80 (dd, J=18.5, 8.0 Hz, 1H); 2.53 (quin, J=8.0 Hz, 1H); 1.96 (d, J=18.5 Hz, 1H); 1.43 (s, 3H); 1.35 (s, 3H); 1.05 (d, J=7.5 Hz, 3H).

1. temperatureThe mixture was warmed to 0° C.
2. temperaturewarming to ambient temperature over 1 hour
3. temperatureThe mixture was then cooled to 0° C.
4. customquenched carefully with 25 mL of 15% acetic acid
5. extractionextracted with EtOAc (3×40 mL)
6. washThe combined organics were washed with NH4Cl (50 mL), dilute NH4OH (2×50 mL) and water (50 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated

ORD record

ord-4235e3fc580b42f2976960ea97ab665c

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08629275B2