4-Methylbenzaldehyde → 8-(3-Hydroxy-3-(p-tolyl)propyn-1-yl)-1,4-dioxaspiro[4.5]decan-8-ol

HRID 1802515Notes

Reaction equation

HRID 1802515 reaction equation
[C:1]([C:3]1([OH:13])[CH2:12][CH2:11][C:6]2([O:10][CH2:9][CH2:8][O:7]2)[CH2:5][CH2:4]1)#[CH:2].C([Li])CCC.[C:19]1([CH3:27])[CH:24]=[CH:23][C:22]([CH:25]=[O:26])=[CH:21][CH:20]=1.[Cl-].[NH4+]>O1CCCC1>[OH:26][CH:25]([C:22]1[CH:23]=[CH:24][C:19]([CH3:27])=[CH:20][CH:21]=1)[C:2]#[C:1][C:3]1([OH:13])[CH2:12][CH2:11][C:6]2([O:7][CH2:8][CH2:9][O:10]2)[CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 77254-MethylbenzaldehydeHCID 25517Ammonium ChlorideHCID 111059858-Ethynyl-1,4-dioxaspiro[4.5]decan-8-olHCID 178418339Butyllithium

Product 1

HCID 583993588-(3-Hydroxy-3-(p-tolyl)propyn-1-yl)-1,4-dioxaspiro[4.5]decan-8-olYield 71.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 8-ethynyl-1,4-dioxaspiro[4.5]decan-8-ol (Reference Example 1) (15.0 g, 82.3 mmol) in tetrahydrofuran (165 mL), 2.77 M n-butyllithium (solution in n-hexane, 62.4 mL, 172.9 mmol) was added dropwise at −72° C. for 25 minutes, and the obtained solution was stirred at the same temperature for 30 minutes. Thereafter, p-tolualdehyde (10.2 mL, 86.4 mmol) was added dropwise at −72° C. for 5 minutes, and the obtained solution was stirred at the same temperature for 30 minutes. The reaction solution was allowed to warm to room temperature and poured into saturated aqueous ammonium chloride solution. The reaction solution was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, n-hexane/ethyl acetate) to obtain the captioned compound (17.7 g, 58.5 mmol, 71%) as an amorphous product.

Workup

  1. stirringthe obtained solution was stirred at the same temperature for 30 minutes
  2. extractionThe reaction solution was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography (silica gel, n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-c78dccd1bae4486e8092a72005327a66
Source dataset
uspto-grants-2013_01
Patent number
US08349874B2

Reaction notes

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