Hydrochloric Acid → Dimethyl 1,1-difluoro-2-hydroxy-4,8,12-trimethyl-3,7,11-tridecatrienylphosphonate

HRID 1377456Notes

Reaction equation

HRID 1377456 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][CH:14]([P:16](=[O:21])([O:19][CH3:20])[O:17][CH3:18])[F:15].[CH3:22][C:23]([CH3:37])=[CH:24][CH2:25][CH2:26]/[C:27](/[CH3:36])=[CH:28]/[CH2:29][CH2:30]/[C:31](/[CH3:35])=[CH:32]/[CH:33]=[O:34].Cl>O1CCCC1>[F:13][C:14]([P:16](=[O:21])([O:19][CH3:20])[O:17][CH3:18])([F:15])[CH:33]([OH:34])[CH:32]=[C:31]([CH3:35])[CH2:30][CH2:29][CH:28]=[C:27]([CH3:36])[CH2:26][CH2:25][CH:24]=[C:23]([CH3:22])[CH3:37]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 5280598(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienalHCID 13426240Dimethyl difluoromethylphosphonateHCID 178418339Butyllithium

Product 1

HCID 54561178Dimethyl 1,1-difluoro-2-hydroxy-4,8,12-trimethyl-3,7,11-tridecatrienylphosphonateYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

Combine diisopropylamine (22.24 mL, 0.159 mol) with tetrahydrofuran (250 mL) and cool to -20° C. Add n-butyllithium (63.3 mL, 2.5N in hexane, 0.159 mol) dropwise to the solution. Stir for 30 minutes and cool to -78° C. Add dropwise a solution of dimethyl difluoromethylphosphonate (25.8 g, 0.159 mol) in tetrahydrofuran (20 mL) while maintaining the temperature below -75° C. After addition is complete, stir for 2 minutes and then slowly add a solution of trans, trans-farnesal [prepared according to Biller, S. A; Forster, C. Tetrahedron 1990, 46(19), 6645](14 g, 0.0636 mol) prepared in step a above, in tetrahydrofuran (10 mL) maintaining the temperature below -72° C. After addition is complete, stir for an additional 2 hours at -78° C. and then pour the reaction into 0.1N hydrochloric acid (500 mL). Extract the reaction with diethyl ether (2×1L). Combine the organic phases, dry over anhydrous magnesium sulfate, filter and concentrate under vacuum. Purify the residue by flash chromatography [40% ethyl acetate/hexane, Rf (50% ethyl acetate/hexane)=0.44] to provide the title compound (9.3 g, 39%) as an oil.

Workup

  1. temperaturewhile maintaining the temperature below -75° C
  2. additionAfter addition
  3. stirringstir for 2 minutes
  4. customprepared
  5. temperaturemaintaining the temperature below -72° C
  6. additionAfter addition
  7. stirringstir for an additional 2 hours at -78° C.
  8. additionpour
  9. extractionExtract
  10. customthe reaction with diethyl ether (2×1L)
  11. dry with materialCombine the organic phases, dry over anhydrous magnesium sulfate
  12. filtrationfilter
  13. concentrationconcentrate under vacuum
  14. customPurify the residue by flash chromatography [40% ethyl acetate/hexane, Rf (50% ethyl acetate/hexane)=0.44]

Sources & evidence

ORD record
ord-a8935cee528e4dd4ada8fc3bda6bfa1f
Source dataset
uspto-grants-1997_09
Patent number
US05665715

Reaction notes

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