Methyl iodide → (2SR,9aSR)-9a-butyl-2,4-dimethyl-7-methoxymethoxy-1,2,9,9a-tetrahydro-3H-fluoren-3-one

HRID 7859

Reaction equation

HRID 7859 reaction equation
[CH2:1]([C:5]12[CH2:17][CH2:16][C:15](=[O:18])[C:14]([CH3:19])=[C:13]1[C:12]1[C:7](=[CH:8][C:9]([O:20][CH2:21][O:22][CH3:23])=[CH:10][CH:11]=1)[CH2:6]2)[CH2:2][CH2:3][CH3:4].[Li+].[CH3:25]C([N-]C(C)C)C.C(=O)=O.CC(C)=O.IC.[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[CH2:1]([C:5]12[CH2:17][CH:16]([CH3:25])[C:15](=[O:18])[C:14]([CH3:19])=[C:13]1[C:12]1[C:7](=[CH:8][C:9]([O:20][CH2:21][O:22][CH3:23])=[CH:10][CH:11]=1)[CH2:6]2)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 18522661Acetone cardiceHCID 219908939a-butyl-7-methoxymethoxy-4-methyl-1,2,9,9a-tetrahydro-3H-fluoren-3-one

Product 1

HCID 67401243(2SR,9aSR)-9a-butyl-2,4-dimethyl-7-methoxymethoxy-1,2,9,9a-tetrahydro-3H-fluoren-3-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 9a-butyl-7-methoxymethoxy-4-methyl-1,2,9,9a-tetrahydro-3H-fluoren-3-one (162 mg, 0.52 mmol) in anhydrous THF (2.5 mL) was cooled in an ice bath and stirred under a nitrogen atmosphere while 0.4M LDA in THF (1.55 mL, 0.62 mmol) was added by syringe. After stirring at 0° C. for 30 minutes, the solution was cooled to −78° C. (dry ice-acetone bath) and treated with iodomethane (0.162 mL, 2.6 mmol). The resulting mixture was allowed to slowly warm to room temperature, then stirred at room temperature overnight. The mixture was diluted with EtOAc (60 mL) and shaken with saturated aqueous NH4Cl (40 mL). The aqueous phase was extracted with more EtOAc (20 mL). The combined organics were washed with 5% NaHCO3, water, and brine, dried over MgSO4, filtered, and concentrated under vacuum to a yellow oil. The crude product was purified by preparative layer chromatography (PLC) on a 0.1×20×20 cm silica gel GF plate using 4:1 hexanes-EtOAc as developing solvent. The band at Rf 0.44-0.56 was extracted with EtOAc and the extracts evaporated under vacuum to provide (2SR,9aSR)-9a-butyl-2,4-dimethyl-7-methoxymethoxy-1,2,9,9a-tetrahydro-3H-fluoren-3-one (111 mg) as an oil.

Workup

  1. additionwas added by syringe
  2. temperatureto slowly warm to room temperature
  3. stirringstirred at room temperature overnight
  4. extractionThe aqueous phase was extracted with more EtOAc (20 mL)
  5. washThe combined organics were washed with 5% NaHCO3, water, and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum to a yellow oil
  9. customThe crude product was purified by preparative layer chromatography (PLC) on a 0.1×20×20 cm silica gel GF plate
  10. extractionThe band at Rf 0.44-0.56 was extracted with EtOAc
  11. customthe extracts evaporated under vacuum

Sources & evidence

ORD record
ord-95e98eaea1a94f0591c92261b6aa3074
Source dataset
uspto-grants-2006_08
Patent number
US07087599B2

Linked notes

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