Hydrochloric Acid → Spiro[isochroman-4,4'-piperidine]

HRID 1182731Notes

Reaction equation

HRID 1182731 reaction equation
[C:1]1([C:7]2([CH2:13][OH:14])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C=O.O1CCOC[CH2:18]1.Cl>C(OCC)(=O)C>[NH:10]1[CH2:9][CH2:8][C:7]2([C:1]3[C:2](=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:18][O:14][CH2:13]2)[CH2:12][CH2:11]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 312751,4-DioxaneHCID 778964-Phenylpiperidine-4-methanol

Product 1

HCID 10847614Spiro[isochroman-4,4'-piperidine]Yield 50%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (4-phenyl-piperidin-4-yl)-methanol (0.1 g, 0.5 mmol), paraformaldehyde (0.11 g, 3.7 mmol), 1,4-dioxane (5 ml) and concentrated hydrochloric acid solution (1.3 ml) was heated at reflux for 80 h. The reaction mixture was diluted with ethyl acetate (100 ml) and washed with 0.5 M aqueous sodium hydroxide solution. The aqueous layer was extracted with ethyl acetate (100 ml). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. Flash chromatography of the crude product with dichloromethane/methanol as eluent gave the title compound (0.053 g, 50%) as yellow solid. MS m/e: 204 (M+H+).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 80 h
  3. washwashed with 0.5 M aqueous sodium hydroxide solution
  4. extractionThe aqueous layer was extracted with ethyl acetate (100 ml)
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fbe554137b2e49738e06414efffe3b1d
Source dataset
uspto-grants-2014_03
Patent number
US08664216B2

Reaction notes

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