Boron trifluoride etherate → 1,3,3-trimethyl-3H-spiro[isobenzofuran-1,4-piperidine]

HRID 899251Notes

Reaction equation

HRID 899251 reaction equation
O[C:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1([OH:18])[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]1)([CH3:4])[CH3:3].B(F)(F)F.CCOCC>C1C=CC=CC=1>[CH3:17][N:14]1[CH2:13][CH2:12][C:11]2([C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[C:2]([CH3:3])([CH3:4])[O:18]2)[CH2:16][CH2:15]1

Participants

4

Reactant 2

HCID 8000Boron trifluoride etherateHCID 122896704-[2-(1-Hydroxy-1-methylethyl)phenyl]-1-methylpiperidin-4-ol

Product 1

HCID 122896791,3,3-trimethyl-3H-spiro[isobenzofuran-1,4-piperidine]Yield 56%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

To a stirred solution of 4-[2-(1-hydroxy-1-methylethyl)phenyl]-1-methylpiperidin-4-ol (step 2, 4.62 g, 18.5 mmol) in benzene (200 mL) was added dropwise boron trifluoride diethyl etherate (11.0 mL, 86.8 mmol) at room temperature and the mixture was stirred for 40 h at the same temperature. The reaction mixture was quenched by the addition of water (200 mL) and 2 N sodium hydroxide aqueous solution (200 mL), and the benzene layer was separated. The aqueous layer was extracted with diethyl ether, and then combined organic layer washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by column chromatography on an amine coated silica gel (100 g) eluting with dichloromethane to afford 2.39 g (56%) of the title compound as a colorless solid:

Workup

  1. customThe reaction mixture was quenched by the addition of water (200 mL) and 2 N sodium hydroxide aqueous solution (200 mL)
  2. customthe benzene layer was separated
  3. extractionThe aqueous layer was extracted with diethyl ether
  4. washcombined organic layer washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe residue was purified by column chromatography on an amine coated silica gel (100 g)
  8. washeluting with dichloromethane

Sources & evidence

ORD record
ord-c9b6f04ef06e4646baf5c79aecbb378c
Source dataset
uspto-grants-2008_04
Patent number
US07354925B2

Reaction notes

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