Water → 4-[2-Methoxyethenyl]-1-phenylbicyclo[2.2.2]octane

HRID 2353070Notes

Reaction equation

HRID 2353070 reaction equation
[Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:24][Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:34]1([C:40]23[CH2:47][CH2:46][C:43](C=O)([CH2:44][CH2:45]2)[CH2:42][CH2:41]3)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.O>C1COCC1>[CH3:2][O:3][CH:4]=[CH:24][C:43]12[CH2:46][CH2:47][C:40]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)([CH2:45][CH2:44]1)[CH2:41][CH2:42]2

Participants

6

Reactant 4

HCID 962WaterHCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 2733832Lithium HexamethyldisilazideHCID 593797914-Phenylbicyclo[2.2.2]octane-1-carboxaldehyde2×

Product 1

HCID 674145044-[2-Methoxyethenyl]-1-phenylbicyclo[2.2.2]octaneYield 102.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To an ice water cooled stirred suspension of (methoxymethyl)triphenylphosphonium chloride (17 g, 49.57 mmol) in anhydrous THF (100 mL) under nitrogen was added lithium bis(trimethylsilyl)amide (1M solution in THF; 50 mL, 50 mmol), and the reaction mixture was allowed to stir at 0° C. for 30 mins. 1-Phenylbicyclo[2.2.2]octane-4-carbaldehyde (Intermediate 6; 10.52 g, 49.08 mmol) in THF (20 mL) was added dropwise and the reaction mixture was allowed to stir at 0° C. for one hour and then at ambient temperature overnight. Water (100 mL) was added and the reaction mixture was partitioned between EtOAc (200 mL) and brine (100 mL), the organic phase was washed with an additional 100 mL of brine then separated, dried (MgSO4) and concentrated to leave a pale yellow gum. The residue was purified on a 330 g Presearch silica cartridge, loading in isohexane/DCM and eluting 0-20% EtOAc-isohexane to provide the title compound as a pale yellow oil (12.6 g, 50.19 mmol, 100%) as a 1:2 mixture of E:Z isomers; E isomer 1H NMR (CDCl3) δ 1.60-1.65 (2H, m), 1.82-1.88 (10H, m), 3.49 (3H, s), 4.74 (1H, d), 6.18 (1H, d), 7.12-7.18 (1H, m), 7.25-7.34 (4H, m); Z isomer: 1H NMR (CDCl3) δ 1.60-1.65 (2H, m), 1.82-1.88 (10H, m), 3.54 (3H, s), 4.09 (1H, d), 5.71 (1H, d), 7.12-7.18 (1H, m), 7.25-7.34 (4H, m); MS (same for both individual isomers): GC-MS EI+ m/e 242 (M+).

Workup

  1. stirringto stir at 0° C. for 30 mins
  2. stirringto stir at 0° C. for one hour
  3. customat ambient temperature
  4. customovernight
  5. customthe reaction mixture was partitioned between EtOAc (200 mL) and brine (100 mL)
  6. washthe organic phase was washed with an additional 100 mL of brine
  7. customthen separated
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customto leave a pale yellow gum
  11. customThe residue was purified on a 330 g Presearch silica cartridge, loading in isohexane/DCM
  12. washeluting 0-20% EtOAc-isohexane

Sources & evidence

ORD record
ord-221b492e68c44baaa761bd5701dc0591
Source dataset
uspto-grants-2010_07
Patent number
US07749997B2

Reaction notes

Loading…