Hydrochloric Acid → Cyclohexyl(5-fluoro-3-methyl-1-benzofuran-2-yl)methanol

HRID 2091025Notes

Reaction equation

HRID 2091025 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10](N(OC)C)=[O:11])=[C:7]([CH3:16])[C:6]=2[CH:17]=1.[C:18]1(C)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[H-].C([Al+]CC(C)C)C(C)C.Cl.O1CCCC1.C1([Mg]Br)CCCCC1.[Cl-].[NH4+]>O1CCCC1>[CH:18]1([CH:10]([C:8]2[O:9][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:17][C:6]=3[C:7]=2[CH3:16])[OH:11])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 550277455-fluoro-N-methoxy-N,3-dimethyl-1-benzofuran-2-carboxamideHCID 86583787Diisobutylaluminumhydride tolueneHCID 178420632HCID 178420632, compound

Product 1

HCID 66777937Cyclohexyl(5-fluoro-3-methyl-1-benzofuran-2-yl)methanolYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution (80 mL) of 5-fluoro-N-methoxy-N,3-dimethyl-1-benzofuran-2-carboxamide (4.37 g) synthesized above in tetrahydrofuran was added dropwise 1.5M diisobutylaluminum hydride toluene solution (24.5 mL) at 0° C., and the mixture was stirred for 1 hr. 1N Hydrochloric acid was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:9, volume ratio) to give a pale-brown solid. To a solution (50 mL) of the obtained solid in tetrahydrofuran was added dropwise 1.0M cyclohexylmagnesium bromide tetrahydrofuran solution (21.8 mL) at 0° C., and the mixture was stirred for 1 hr. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:17, volume ratio) to give the title object compound (1.32 g, 27%) as a pale-yellow oil.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:9, volume ratio)
  8. customto give a pale-brown solid
  9. stirringthe mixture was stirred for 1 hr
  10. customto quench
  11. customthe reaction
  12. extractionthe mixture was extracted with ethyl acetate
  13. washThe extract was washed with saturated brine
  14. dry with materialdried over magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:17, volume ratio)

Sources & evidence

ORD record
ord-6240719d9614444f9a51830195f41d9a
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

Loading…