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

HRID 888289Notes

Reaction equation

HRID 888289 reaction equation
[CH2:1]([O:8][CH2:9][C:10]1([C:20]#[CH:21])[CH2:19][CH2:18][C:13]2([O:17][CH2:16][CH2:15][O:14]2)[CH2:12][CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[CH3:27][C:28]1[CH:35]=[CH:34][C:31]([CH:32]=[O:33])=[CH:30][CH:29]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:1]([O:8][CH2:9][C:10]1([C:20]#[C:21][CH:32]([C:31]2[CH:34]=[CH:35][C:28]([CH3:27])=[CH:29][CH:30]=2)[OH:33])[CH2:19][CH2:18][C:13]2([O:14][CH2:15][CH2:16][O:17]2)[CH2:12][CH2:11]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 77254-MethylbenzaldehydeHCID 25517Ammonium ChlorideHCID 58399414HCID 58399414, compoundHCID 178418339Butyllithium

Product 1

HCID 583994443-(8-(Benzyloxymethyl)-1,4-dioxaspiro[4.5]decan-8-yl)-1-(p-tolyl)propyn-1-olYield 82.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 8-(benzyloxymethyl)-8-ethynyl-1,4-dioxaspiro[4.5]decane (Reference Example 87) (393 mg, 1.37 mmol) in tetrahydrofuran (4.6 mL), 2.6 M n-butyllithium (solution in hexane, 0.555 mL, 1.44 mmol) was added at −78° C., and the obtained solution was stirred for 10 minutes. Further, 4-methylbenzaldehyde (0.178 mL, 1.51 mmol) was added, and the obtained solution was allowed to warm gradually to room temperature and stirred for 1 hour. Saturated aqueous ammonium chloride solution was added to the reaction solution, and the resulting 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 (459 mg, 1.13 mmol, 82%) as a colorless oily compound.

Workup

  1. stirringstirred for 1 hour
  2. extractionthe resulting 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-6b756b6789b741c1b6e19a6a0b15887c
Source dataset
uspto-grants-2012_08
Patent number
US08247569B2

Reaction notes

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