Triethylamine → 1'-Benzylspiro[isochroman-1,4'-piperidine]

HRID 1182728Notes

Reaction equation

HRID 1182728 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:21][CH2:22]O)([OH:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O>>[CH2:1]([N:8]1[CH2:9][CH2:10][C:11]2([C:15]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:21][CH2:22][O:14]2)[CH2:12][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 673640824-[2-(Hydroxyethyl)phenyl]-1-benzylpiperidin-4-ol

Product 1

HCID 102664131'-Benzylspiro[isochroman-1,4'-piperidine]Yield 21%

Procedure

To a solution of 1-benzyl-4-[2-(2-hydroxy-ethyl)-phenyl]-piperidin-4-ol (2.0 g, 6.6 mmol) and triethylamine (1.9 ml, 14 mmol) dry tetrahydrofuran (50 ml) was added methanesulfonyl chloride (0.48 ml, 6.2 mmol) at room temperature. The reaction mixture was heated at reflux for 4 h. Quenching with water and basification with 1 M aqueous sodium hydroxide solution was followed by extraction with three portions of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. Flash chromatography of the crude product with n-heptane/ethyl acetate as eluent gave the title compound (0.40 g, 21%) as yellow oil. MS m/e: 294 (M+H+).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 4 h
  3. customQuenching with water and basification with 1 M aqueous sodium hydroxide solution
  4. extractionwas followed by extraction with three portions of ethyl acetate
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8920f10f20f44dcf930392ae95ba2f28
Source dataset
uspto-grants-2014_03
Patent number
US08664216B2

Reaction notes

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