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

HRID 2386992Notes

Reaction equation

HRID 2386992 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]1[C:17]2([CH2:22][CH2:21][CH2:20][CH2:19][C:18]2=[O:23])[CH2:16][CH2:15][CH2:14]1.[C:24](=O)([O:27]C)[O:25][CH3:26]>CCOCC>[O:23]=[C:18]1[CH:19]([C:24]([O:25][CH3:26])=[O:27])[CH2:20][CH2:21][CH2:22][C:17]21[CH2:13][CH2:14][CH2:15][CH2:16]2

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 12021Dimethyl CarbonateHCID 290662Spiro(4.5)decan-6-oneHCID 178418339Butyllithium

Product 1

HCID 57429459Methyl 6-oxospiro[4.5]decane-7-carboxylate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

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 10A (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 ammonium chloride 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 magnesium sulfate, and concentrated under reduced pressure. The residue was chromatographed on silica gel (100% hexane to 85:15 ethyl acetate/hexanes, eluant) to provide the title product. 1H NMR (300 MHz, CDCl3) δ 12.40-12.42 (m, 1H), 3.72-3.76 (m, 3H), 2.18-2.26 (m, 2H), 2.00-2.12 (m, 2H), 1.74-1.86 (m, 2H), 1.57-1.62 (m, 2H), 1.54-1.57 (m, 2H), 1.35-1.48 (m, 4H); MS (DCI+) m/z 211 (M+H)+.

Workup

  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 ammonium chloride
  6. additiondiluted with ether (100 mL)
  7. customthen the layers were separated
  8. extractionThe aqueous layer was extracted with additional ether
  9. dry with materialdried with magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was chromatographed on silica gel (100% hexane to 85:15 ethyl acetate/hexanes, eluant)

Sources & evidence

ORD record
ord-0ef63241f4bc4e608220427d0db26808
Source dataset
uspto-grants-2012_09
Patent number
US08268846B2

Reaction notes

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