Water → HCID 178520736, compound

HRID 1674444Notes

Reaction equation

HRID 1674444 reaction equation
[CH:1]([C@H:3]1[CH2:8][CH2:7][C@H:6]([CH2:9][O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=2[F:18])[CH2:5][CH2:4]1)=O.[Cl-].[CH3:20][O:21]C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[K+].O>C1COCC1>[CH:20]([CH2:1][C@H:3]1[CH2:8][CH2:7][C@H:6]([CH2:9][O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=2[F:18])[CH2:5][CH2:4]1)=[O:21]

Participants

6

Reactant 4

HCID 962WaterHCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 23665647Potassium tert-butoxideHCID 178520953HCID 178520953, compound

Product 1

HCID 178520736HCID 178520736, compoundYield 67.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

11.5 g of 1-((trans-4-formylcyclohexyl)methoxy)-2,3-difluorobenzene was dissolved in 50 mL of THF, and 18.6 g of methoxymethyl triphenylphosphonium chloride was added thereto. To this solution, the THF (20 mL) solution containing 6.1 g of potassium-t-butoxide was added dropwise at an internal temperature of 5 to 20° C., and the solution was stirred for 30 min. 10 mL of water was added thereto, and the solvent was evaporated under reduced pressure. Hexane and 50% methanol aqueous solution were added thereto, and the organic layer was fractioned. This organic layer was washed with 50% methanol aqueous solution and saturated saline, and subjected to column chromatography. After evaporating the solvent under reduced pressure, the residue was dissolved in 70 mL of THF, and 70 mL of 10% hydrochloric acid was added thereto, followed by reflux with heating for 2 hours. To the solution, water and ethyl acetate were added, and the organic layer was fractioned, washed with saturated saline 3 times, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, to thereby obtain 8.2 g of 1-((trans-4-(formylmethyl)cyclohexyl)methoxy)-2,3-difluorobenzene.

Workup

  1. additionwas added dropwise at an internal temperature of 5 to 20° C.
  2. customthe solvent was evaporated under reduced pressure
  3. additionHexane and 50% methanol aqueous solution were added
  4. washThis organic layer was washed with 50% methanol aqueous solution and saturated saline
  5. customAfter evaporating the solvent under reduced pressure
  6. dissolutionthe residue was dissolved in 70 mL of THF
  7. addition70 mL of 10% hydrochloric acid was added
  8. temperatureby reflux
  9. temperaturewith heating for 2 hours
  10. additionTo the solution, water and ethyl acetate were added
  11. washwashed with saturated saline 3 times
  12. dry with materialdried over anhydrous sodium sulfate
  13. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-4a93d86a70ec4988b2e03ab3422bf612
Source dataset
uspto-grants-2011_08
Patent number
US08003006B2

Reaction notes

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