3,4-dihydro-2H-pyran → Methyl 3-bromo-4-(tetrahydro-2H-pyran-2-yloxy)benzoate

HRID 1662365Notes

Reaction equation

HRID 1662365 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[OH:12])[C:5]([O:7][CH3:8])=[O:6].[O:13]1[CH:18]=[CH:17][CH2:16][CH2:15][CH2:14]1.O.CC1C=CC(S(O)(=O)=O)=CC=1>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH:14]1[CH2:15][CH2:16][CH2:17][CH2:18][O:13]1)[C:5]([O:7][CH3:8])=[O:6]

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 4778958Methyl 3-bromo-4-hydroxybenzoate

Product 1

HCID 57467623Methyl 3-bromo-4-(tetrahydro-2H-pyran-2-yloxy)benzoateYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 66.6E (38 g, 164 mmol) and 3,4-dihydro-2H-pyran (45 mL, 493 mmol) in DCM (355 mL,) was added 4-methylbenzenesulfonic acid hydrate (0.63 g, 3.30 mmol). The mixture was stirred at room temperature and monitored by TLC. After 2 hours, the solution was washed with a mixed aqueous solution of saturated aqueous sodium bicarbonate/brine/water (1:1:2). The aqueous layer was extracted three times with ether. After drying over anhydrous sodium sulfate and then filtering, the organic solvent was removed under reduced pressure. The crude material was purified on silica gel (0-10% EtOAc in hexanes) to yield a white solid. The product was recrystallized from MeOH to provide 66.6F (yield 90%). 1H NMR (400 MHz, CDCl3) δ ppm 8.24 (1H, d, J=2.0 Hz), 7.93 (1H, dd, J=8.6, 2.0 Hz), 7.17 (1H, d, J=8.6 Hz), 5.62 (1H, t, J=2.5 Hz), 3.90 (3H, s), 3.83 (1H, td, J=11.1, 2.9 Hz), 3.66 (1H, m), 2.18 (1H, m), 2.04 (1H, m), 1.94 (1H, m), 1.79 (2H, m), 1.67 (1H, m).)

Workup

  1. washthe solution was washed with a mixed aqueous solution of saturated aqueous sodium bicarbonate/brine/water (1:1:2)
  2. extractionThe aqueous layer was extracted three times with ether
  3. dry with materialAfter drying over anhydrous sodium sulfate
  4. filtrationfiltering
  5. customthe organic solvent was removed under reduced pressure
  6. customThe crude material was purified on silica gel (0-10% EtOAc in hexanes)
  7. customto yield a white solid
  8. customThe product was recrystallized from MeOH

Sources & evidence

ORD record
ord-1497510dad4b4f3c8cd261061998d85e
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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