Diisopropylamine → Methyl 6-oxospiro[4.5]decane-7-carboxylate

Temperature

-78 °C

A solution of diisopropylamine (5.97 mL, 41.9 mmol) in ether (30 mL) was cooled to −78° C. and then was treated slowly with n-butyllithium (16.75 mL, 41.9 mmol). The mixture was stirred at −78° C. for 30 minutes, then this solution was transferred via cannula into a −78° C. solution of Example 1A (4.25 g, 27.9 mmol) in ether (30 mL). The mixture was stirred at this temperature for 30 minutes and then was treated with dimethyl carbonate (23.50 mL, 279 mmol). The resulting mixture was warmed to ambient temperature and stirred for 16 hours. The mixture was quenched with saturated NH4Cl and diluted with ether (100 mL), then the layers were separated. The aqueous layer was extracted with additional ether, then the organic layers were combined, dried with MgSO4, and concentrated under reduced pressure. The residue was chromatographed on silica gel (100% hexane to 85:15 EtOAc/hexanes, eluant) to provide the title product. 1H NMR (300 MHz, CDCl3) δ 12.40-12.42 (m, 1 H), 3.72-3.76 (m, 3 H), 2.18-2.26 (m, 2 H), 2.00-2.12 (m, 2 H), 1.74-1.86 (m, 2 H), 1.57-1.62 (m, 2 H), 1.54-1.57 (m, 2 H), 1.35-1.48 (m, 4 H). MS (DCI+) m/z 211 (M+H).

1. customwas transferred via cannula into a −78° C.
2. stirringThe mixture was stirred at this temperature for 30 minutes
3. temperatureThe resulting mixture was warmed to ambient temperature
4. stirringstirred for 16 hours
5. customThe mixture was quenched with saturated NH4Cl
6. additiondiluted with ether (100 mL)
7. customthe layers were separated
8. extractionThe aqueous layer was extracted with additional ether
9. dry with materialdried with MgSO4
10. concentrationconcentrated under reduced pressure
11. customThe residue was chromatographed on silica gel (100% hexane to 85:15 EtOAc/hexanes, eluant)

ORD record

ord-5e0c0685baf944faa1538c074c0196b5

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08278313B2