Hydrochloric Acid → 1'-Benzyl-6-chloro-3H-spiro[isobenzofuran-1,4'-piperidine]

HRID 270049Notes

Reaction equation

HRID 270049 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2([C:17]3[CH:18]=[C:19]([Cl:22])[CH:20]=[CH:21][C:16]=3[C:15](=O)[O:14]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B.Cl.[OH-].[Na+]>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2([C:17]3[CH:18]=[C:19]([Cl:22])[CH:20]=[CH:21][C:16]=3[CH2:15][O:14]2)[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6331BoraneHCID 14798Sodium HydroxideHCID 122130471'-Benzyl-6-chloro-3H-spiro[2-benzofuran-1,4'-piperidin]-3-one

Product 1

HCID 598336401'-Benzyl-6-chloro-3H-spiro[isobenzofuran-1,4'-piperidine]Yield 85.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1′-benzyl-6-chloro-3H-spiro[2-benzofuran-1,4′-piperidine]-3-one (1.1 g, 3.35 mmol) in THF (15 mL) was added 1 M solution of borane (Marxer, A; Rodriguez, H. R; McKenna, J. M; Tsai, H. M., J. Org. Chem., 1975, 40, 1427-1430) complex in THF (7 mL, 7.0 mmol) slowly at 0° C. After addition was complete, the reaction mixture was kept at room temperature for 30 minutes (min), then kept at reflux overnight, cooled to 0° C. and 6M aqueous hydrochloric acid (HCl) (3.5 mL) was added slowly. The reaction mixture was kept at reflux for 5 h, cooled to 0° C., pH of the reaction mixture was adjusted to 10 by addition of aqueous NaOH 6M and the whole was extracted with ethyl acetate. The organic layer was washed with H2O, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel flash chromatography (0-30% ethyl acetate in petroleum ether) to give the sub-titled compound (900 mg).

Workup

  1. customslowly at 0° C
  2. additionAfter addition
  3. temperatureat reflux overnight
  4. temperatureat reflux for 5 h
  5. temperaturecooled to 0° C.
  6. extractionthe whole was extracted with ethyl acetate
  7. washThe organic layer was washed with H2O
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by silica gel flash chromatography (0-30% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-48d79ac957244662a374a36991338cf2
Source dataset
uspto-grants-2008_11
Patent number
US07449475B2

Reaction notes

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