4-Hydroxybenzaldehyde → 4-(2-Tetrahydro-2H-pyranoxy)benzaldehyde

HRID 1827513Notes

Reaction equation

HRID 1827513 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[O:10]1[CH:15]=[CH:14][CH2:13][CH2:12][CH2:11]1>C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.C(Cl)Cl>[O:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH:11]1[O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 1264-HydroxybenzaldehydeHCID 80803,4-dihydro-2H-pyran

Product 1

HCID 112527364-(2-Tetrahydro-2H-pyranoxy)benzaldehydeYield 102.6%

Reagents, catalysts & solvents 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)CatalystHCID 6344DichloromethaneSolvent

Procedure

To 4-hydroxybenzaldehyde (10.0 g, 81.89 mmol) was added 175 mL methylene chloride, 3,4-dihydro-2H-pyran (18.7 mL, 204.97 mmol) and pyridinium p-toluenesulfonate (2.06 g, 8.2 mmol). The reaction mixture was stirred at room temperature for three days. The reaction mixture was partitioned between methylene chloride and saturated aqueous sodium bicarbonate. The layers were separated and the aqueous layer was extracted with a second portion of methylene chloride. The combined organic layers were washed with saturated aqueous sodium chloride, which was then back-extracted with methylene chloride. The combined organic layers were dried over sodium sulfate, filtered, and concentrated. Silica gel flash chromatography of the residue (10% ether/hexanes to 20% ether/hexanes) afforded 17.32 g of the title compound of Step A. MS 207.4 (M+1)+Step B: [4-(2-Pyrrolidin-1-yl-ethoxy)-phenyl]-[4-(tetrahydro-pyran-2-yloxy)-benzyl]-amine

Workup

  1. customThe reaction mixture was partitioned between methylene chloride and saturated aqueous sodium bicarbonate
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with a second portion of methylene chloride
  4. washThe combined organic layers were washed with saturated aqueous sodium chloride, which
  5. extractionwas then back-extracted with methylene chloride
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-14489c46aca54ac5b338610ad613d788
Source dataset
uspto-grants-2006_05
Patent number
US07053212B2

Reaction notes

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