Hydrochloric Acid → 8-(3,5-Difluorophenyl)-1,4-dioxaspiro[4.5]decan-8-ol

HRID 1406830Notes

Reaction equation

HRID 1406830 reaction equation
[Mg].[F:2][C:3]1[CH:4]=[C:5](Br)[CH:6]=[C:7]([F:9])[CH:8]=1.[CH2:11]1[O:21][C:14]2([CH2:19][CH2:18][C:17](=[O:20])[CH2:16][CH2:15]2)[O:13][CH2:12]1.Cl>C1COCC1.C1(C)C=CC=CC=1.O>[CH2:12]1[O:13][C:14]2([CH2:19][CH2:18][C:17]([C:5]3[CH:4]=[C:3]([F:2])[CH:8]=[C:7]([F:9])[CH:6]=3)([OH:20])[CH2:16][CH2:15]2)[O:21][CH2:11]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 1363131-Bromo-3,5-difluorobenzeneHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 5462224Magnesium

Product 1

HCID 573701578-(3,5-Difluorophenyl)-1,4-dioxaspiro[4.5]decan-8-olYield 102.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

In an argon atmosphere, 20.3 g of magnesium was suspended in THF (40 mL), and a solution of 3,5-difluorobromobenzene (149 g) in THF (450 mL) was added dropwise to the resultant suspension at an inside temperature of 40 to 65° C. After stirring at room temperature for 1 hour, a solution of 1,4-cyclohexanedione monoethylene ketal (100 g) in THF (300 mL) was added dropwise at an inside temperature of 40 to 60° C., followed by stirring at room temperature for 1 hour. Then, water (250 mL), 10% hydrochloric acid (200 mL), and 750 mL of toluene were added in that order, and the mixture was stirred at room temperature for 30 minutes to separate an organic layer. The organic layer was washed with saturated brine two times, and then dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to yield 178 g of 4-(3,5-difluorophenyl)-4-hydroxycyclohexanone ethylene ketal as a light yellow solid.

Workup

  1. stirringby stirring at room temperature for 1 hour
  2. stirringthe mixture was stirred at room temperature for 30 minutes
  3. customto separate an organic layer
  4. washThe organic layer was washed with saturated brine two times
  5. dry with materialdried with anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-bfc67301c8c84ee6a37b9f54bc882be3
Source dataset
uspto-grants-2014_12
Patent number
US08916718B2

Reaction notes

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