Water → HCID 178520953, compound

HRID 1674443Notes

Reaction equation

HRID 1674443 reaction equation
O=[C:2]1[CH2:7][CH2:6][CH:5]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:11]=2[F:17])[CH2:4][CH2:3]1.[Cl-].[CH3:19][O:20]C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[K+].O>C1COCC1>[CH:19]([C@H:2]1[CH2:7][CH2:6][C@H:5]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:11]=2[F:17])[CH2:4][CH2:3]1)=[O:20]

Participants

6

Reactant 4

HCID 962WaterHCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 23665647Potassium tert-butoxideHCID 57815776HCID 57815776, compound

Product 1

HCID 178520953HCID 178520953, compoundYield 78.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

13.8 g of 1-((4-oxocyclohexyl)methoxy)-2,3-difluorobenzene was dissolved in 50 mL of THF, and 23.6 g of methoxymethyl triphenylphosphonium chloride was added thereto. To this solution, the THF (20 mL) solution containing 7.7 g of potassium-t-butoxide was added dropwise at an internal temperature of 10 to 25° C., and the solution was stirred for 30 nm. 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 100 mL of THF, and 100 mL of 10% hydrochloric acid was added thereto, followed by reflux with heating for 3 hours. To the solution, water and ethyl acetate were added, and the organic layer was fractioned, washed with saturated saline, saturated sodium hydrogencarbonate, and saturated saline in this order, and dried over anhydrous sodium sulfate. Then, the solvent was evaporated under reduced pressure. To the residue, 30 mL of methanol and 20% sodium hydroxide aqueous solution were added, and the solution was stirred with ice-cooling 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 11.5 g of 1-((trans-4-formylcyclohexyl)methoxy)-2,3-difluorobenzene.

Workup

  1. additionwas added dropwise at an internal temperature of 10 to 25° 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 100 mL of THF
  7. addition100 mL of 10% hydrochloric acid was added
  8. temperatureby reflux
  9. temperaturewith heating for 3 hours
  10. additionTo the solution, water and ethyl acetate were added
  11. washwashed with saturated saline, saturated sodium hydrogencarbonate, and saturated saline in this order
  12. dry with materialdried over anhydrous sodium sulfate
  13. customThen, the solvent was evaporated under reduced pressure
  14. additionTo the residue, 30 mL of methanol and 20% sodium hydroxide aqueous solution were added
  15. stirringthe solution was stirred with ice-
  16. temperaturecooling for 2 hours
  17. additionTo the solution, water and ethyl acetate were added
  18. washwashed with saturated saline 3 times
  19. dry with materialdried over anhydrous sodium sulfate
  20. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-96e2ab8cb7274e87aa6c9210225eb3ec
Source dataset
uspto-grants-2011_08
Patent number
US08003006B2

Reaction notes

Loading…