Hydrochloric Acid → 8-(4-Butoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decan-8-ol

HRID 1886716Notes

Reaction equation

HRID 1886716 reaction equation
[CH2:1]([O:5][C:6]1[C:7]([F:13])=[C:8]([F:12])[CH:9]=[CH:10][CH:11]=1)[CH2:2][CH2:3][CH3:4].C([Li])CCC.[O:19]1[C:23]2([CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]2)[O:22][CH2:21][CH2:20]1.Cl>C1COCC1.C(OCC)(=O)C>[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([C:26]2([OH:29])[CH2:27][CH2:28][C:23]3([O:22][CH2:21][CH2:20][O:19]3)[CH2:24][CH2:25]2)=[C:8]([F:12])[C:7]=1[F:13])[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 27829391-Butoxy-2,3-DifluorobenzeneHCID 178418339Butyllithium

Product 1

HCID 666823378-(4-Butoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decan-8-olYield 99.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

3-Butoxy-1,2-difluorobenzene (7) (30.0 g) and THF (500 ml) were added to a reaction vessel under an atmosphere of nitrogen, and cooled to −74° C. n-Butyllithium (1.66 M in n-hexane solution; 120 ml) was added dropwise in the temperature range of −74° C. to −70° C. and the stirring was continued for another 2 hours. Successively, 1,4-dioxaspiro[4.5]decan-8-one (8) (30.2 g) in THF (200 ml) solution was added dropwise in the temperature range of −75° C. to −70° C., and the stirring was continued for another 8 hours while the mixture was allowed to come to 25° C. The resulting reaction mixture was poured into a 1N—HCl aqueous solution (500 ml) and ethyl acetate (500 ml) in a vessel and mixed with them. The mixture was then allowed to stand until it had separated into organic and aqueous phases, and the extraction into an organic phase was carried out. The resulting organic phase was separated, and washed successively with water, a saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure to leave 8-(4-butoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decan-8-ol (9) (55.0 g). The resulting compound (9) was a pale yellow oil.

Workup

  1. additionwas added dropwise in the temperature range of −74° C. to −70° C.
  2. waitthe stirring was continued for another 8 hours while the mixture
  3. customto come to 25° C
  4. customThe resulting reaction mixture
  5. additionmixed with them
  6. customhad separated into organic and aqueous phases
  7. extractionthe extraction into an organic phase
  8. customThe resulting organic phase was separated
  9. washwashed successively with water
  10. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate
  11. distillationThe solvent was then distilled off under reduced pressure

Sources & evidence

ORD record
ord-69bb668264bc47cb9c49248df04e08dc
Source dataset
uspto-grants-2013_08
Patent number
US08501038B2

Reaction notes

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