Ammonium Chloride → 4-(1,4-Dioxaspiro[4,5]dec-8-yl)-1-(4-ethoxy-2,3-difluorophenyl)cyclohexanol

HRID 1787396Notes

Reaction equation

HRID 1787396 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH3:11])=[C:5]([F:12])[C:4]=1[F:13].[O:14]1[C:18]2([CH2:23][CH2:22][CH:21]([CH:24]3[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]3)[CH2:20][CH2:19]2)[O:17][CH2:16][CH2:15]1.[Cl-].[NH4+]>C1COCC1.C1(C)C=CC=CC=1>[O:14]1[C:18]2([CH2:19][CH2:20][CH:21]([CH:24]3[CH2:29][CH2:28][C:27]([C:3]4[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH3:11])=[C:5]([F:12])[C:4]=4[F:13])([OH:30])[CH2:26][CH2:25]3)[CH2:22][CH2:23]2)[O:17][CH2:16][CH2:15]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 8109134-(1,4-Dioxa-spiro(4.5)dec-8-yl)-cyclohexanoneHCID 5462224MagnesiumHCID 269854911-Bromo-4-ethoxy-2,3-difluorobenzene

Product 1

HCID 597736464-(1,4-Dioxaspiro[4,5]dec-8-yl)-1-(4-ethoxy-2,3-difluorophenyl)cyclohexanolYield 120.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
40 °C

Procedure

First Step: 6.1 g of well dried magnesium and 20 mL of THF were placed in a reactor under nitrogen atmosphere, and heated to 40° C. 59.7 g of 1-bromo-4-ethoxy-2,3-difluorobenzene (1) dissolved in 300 mL of THF was slowly added dropwise thereto at a temperature range of from 40 to 60° C., followed by stirring for 60 minutes. Thereafter, 50.0 g of 4-(1,4-dioxaspiro[4,5]dec-8-yl)cyclohexanone (2) dissolved in 150 mL of THF was slowly added dropwise thereto at a temperature range of from 50 to 60° C., followed by stirring for 60 minutes. After cooling the resulting reaction mixture to 30° C., the reaction mixture was mixed with 900 mL of a 3% ammonium chloride aqueous solution and 500 mL of toluene cooled to 0° C. in a vessel and separated into an organic layer and an aqueous layer by standing still, so as to attain extraction. The resulting organic layer was fractionated and washed with water, a saturated sodium bicarbonate aqueous solution, and water, followed by drying over anhydrous magnesium sulfate. Thereafter, the solvent was distilled off under reduced pressure to obtain 100.1 g of 4-(1,4-dioxaspiro[4,5]dec-8-yl)-1-(4-ethoxy-2,3-difluorophenyl)cyclohexanol (3). The resulting compound (3) was a yellow solid.

Workup

  1. additionwas slowly added dropwise
  2. customof from 40 to 60° C.
  3. additionwas slowly added dropwise
  4. customof from 50 to 60° C.
  5. stirringby stirring for 60 minutes
  6. temperatureAfter cooling
  7. customthe resulting reaction mixture to 30° C.
  8. temperaturecooled to 0° C. in a vessel
  9. customseparated into an organic layer
  10. extractionextraction
  11. washwashed with water
  12. dry with materialby drying over anhydrous magnesium sulfate
  13. distillationThereafter, the solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-7a0364f1f29e4deba1874f3ffb7124bc
Source dataset
uspto-grants-2009_03
Patent number
US07510749B2

Reaction notes

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