Trimethyl borate → HCID 69416314, compound

HRID 1593354Notes

Reaction equation

HRID 1593354 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:6][C:7]3[C:12]([C:13]=2[C:14]=1[F:15])=[CH:11][C:10]([CH2:16][CH2:17][CH3:18])=[CH:9][CH:8]=3.[Li][CH2:20][CH2:21][CH2:22][CH3:23].B(OC)(OC)[O:25]C>C1COCC1>[CH2:20]([O:25][C:3]1[C:2]([F:1])=[C:14]([F:15])[C:13]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([CH2:16][CH2:17][CH3:18])[CH:11]=3)[CH2:6][C:5]=2[CH:4]=1)[CH2:21][CH2:22][CH3:23]

Participants

5

Reactant 3

HCID 8470Trimethyl borateHCID 69416819HCID 69416819, compoundHCID 178418339Butyllithium

Product 1

HCID 69416314HCID 69416314, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 5.2 g of 3,4-difluoro-6-propylfluorene (example 1) in 50 ml of dry THF is cooled to −70° C. and 15 ml of n-BuLi (1.6 m solution in hexane) are added dropwise under a protective gas atmosphere in such a way that the internal temperature is always below −70° C. Subsequently, the mixture is stirred at this temperature for a further 2 h and then 2.7 g of trimethyl borate dissolved in 10 ml of THF are added at the same temperature. The reaction mixture is allowed to come to −10° C., quenched with water and acidified with hydrochloric acid. After extraction with MTBE, the combined organic phases are washed with saturated NaCl solution and dried over sodium sulfate. The crude boronic acid obtained after the removal of the solvent is dissolved in 100 ml of MTBE, heated to boiling, admixed rapidly with 7.5 ml of 35 percent aqueous hydrogen peroxide solution and stirred under reflux for a further 2.5 h. After cooling, the phases are separated, the aqueous phase is extracted once more with MTBE and the combined organic phases are washed successively with water, saturated sodium sulfite solution and saturated NaCl solution. After drying over sodium sulfate and removal of the solvent under reduced pressure, the crude product is purified by column chromatography on silica gel using 9:1 (v/v) heptane/ethyl acetate as the eluent. The resulting 3,4-difluoro-6-propylfluoren-2-ol is heated to boiling with 2.4 g of 1-bromobutane and 5.4 g of potassium carbonate in 120 ml of MEK for 6 h. After cooling, the reaction mixture is added to ice/water and extracted with MTBE, and the organic phases are washed with water and saturated NaCl solution and dried over sodium sulfate. After the solvents have been removed under reduced pressure, the colorless crude product is purified chromatographically on silica gel with 2:8 (v/v) dichloromethane/heptane as the eluent and recrystallized from heptane. 2.7 g of 2-butyloxy-3,4-difluoro-6-propylfluorene are obtained.

Workup

  1. customis always below −70° C
  2. additionare added at the same temperature
  3. customto come to −10° C.
  4. customquenched with water
  5. extractionAfter extraction with MTBE
  6. washthe combined organic phases are washed with saturated NaCl solution
  7. dry with materialdried over sodium sulfate
  8. customThe crude boronic acid obtained
  9. customafter the removal of the solvent
  10. dissolutionis dissolved in 100 ml of MTBE
  11. temperatureheated
  12. stirringstirred
  13. temperatureunder reflux for a further 2.5 h
  14. temperatureAfter cooling
  15. customthe phases are separated
  16. extractionthe aqueous phase is extracted once more with MTBE
  17. washthe combined organic phases are washed successively with water, saturated sodium sulfite solution and saturated NaCl solution
  18. dry with materialAfter drying over sodium sulfate and removal of the solvent under reduced pressure
  19. customthe crude product is purified by column chromatography on silica gel using 9:1 (v/v) heptane/ethyl acetate as the eluent
  20. temperatureThe resulting 3,4-difluoro-6-propylfluoren-2-ol is heated
  21. waitto boiling with 2.4 g of 1-bromobutane and 5.4 g of potassium carbonate in 120 ml of MEK for 6 h
  22. temperatureAfter cooling
  23. additionthe reaction mixture is added to ice/water
  24. extractionextracted with MTBE
  25. washthe organic phases are washed with water and saturated NaCl solution
  26. dry with materialdried over sodium sulfate
  27. customAfter the solvents have been removed under reduced pressure
  28. customthe colorless crude product is purified chromatographically on silica gel with 2:8 (v/v) dichloromethane/heptane as the eluent
  29. customrecrystallized from heptane

Sources & evidence

ORD record
ord-b036ae3976b74c0dbb2de015315a99de
Source dataset
uspto-grants-2007_11
Patent number
US07297379B2

Reaction notes

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