3,4-dihydro-2H-pyran → 2-Chloro-4-(tetrahydro-pyran-2-yloxy)-benzaldehyde

HRID 1827514Notes

Reaction equation

HRID 1827514 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[O:11]1[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12]1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O1CCCC1.O>[Cl:1][C:2]1[CH:9]=[C:8]([O:10][CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16][O:11]2)[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5]

Participants

8

Reactant 4

HCID 80803,4-dihydro-2H-pyran2×HCID 1853632-Chloro-4-hydroxybenzaldehydeHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)2×HCID 516892Sodium Bicarbonate

Product 1

HCID 221373212-Chloro-4-(tetrahydro-pyran-2-yloxy)-benzaldehydeYield 72.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-chloro-4-hydroxybenzaldehyde (12.0 g, 76.64 mmol) in 175 mL methylene chloride and 10 mL tetrahydrofuran was added 3,4-dihydro-2H-pyran (17.5 mL, 191.6 mmol) and pyridinium p-toluenesulfonate (1.93 g, 7.66 mmol). The reaction mixture was stirred at room temperature for 4 days. Additional 3,4-dihydro-2H-pyran (17.0 mL, 186.3 mmol) and pyridinium p-toluenesulfonate (1.85 g, 7.36 mmol) were added, followed by 5A molecular sieves, and the reaction mixture continued to stir at room temperature for 3 days. Saturated aqueous sodium bicarbonate and water were added. The layers were separated and the aqueous layer was extracted with a second portion of methylene chloride. The combined organic layers were dried (sodium sulfate), filtered, and concentrated. Silica gel flash chromatography of the residue (20% ethyl acetate/hexanes to 50% ethyl acetate/hexanes) afforded 13.37 g (72%) of the title compound of Step A. MS 241.0 (M+1)+

Workup

  1. stirringto stir at room temperature for 3 days
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with a second portion of methylene chloride
  4. dry with materialThe combined organic layers were dried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-9d2b46b1200b41808114004851503625
Source dataset
uspto-grants-2006_05
Patent number
US07053212B2

Reaction notes

Loading…