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

HRID 1685657

Reaction equation

HRID 1685657 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[OH:12].[O:13]1[CH:18]=[CH:17][CH2:16][CH2:15][CH2:14]1>C(Cl)Cl.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[O:12][CH:14]1[CH2:15][CH2:16][CH2:17][CH2:18][O:13]1

Participants

5

Reactant 2

HCID 80803,4-dihydro-2H-pyranHCID 6425184Methyl 4-Bromo-3-hydroxybenzoate

Product 1

HCID 16747841Methyl 4-bromo-3-(tetrahydropyran-2-yloxy)benzoateYield 76%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared by adapting the method reported by Kita et al.[Kita, 1994] To a solution of methyl 4-bromo-3-hydroxybenzoate (4.0 g, 17.31 mmol) in anhydrous CH2Cl2 (30 mL) was added 3,4-dihydro-2H-pyran (3.95 mL, 43.28 mmol) and p-toluenesulfonic acid (0.01 g, 0.17 mmol) at 0° C. The mixture was stirred at this temperature for 90 min, warmed to room temperature and quenched with saturated NaHCO3 solution (50 mL). The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The pale yellow residue was purified by flash column chromatography [SiO2, Et2O/n-hexane (4:6)] affording a colourless oil. The oil solidified on standing at room temperature to give methyl 4-bromo-3-(tetrahydropyran-2-yloxy)benzoate as colourless needles (4.12 g, 76%); δH (270 MHz, CDCl3) 1.59-1.77 (m, 3H), 1.86-2.13 (m, 3H), 3.6-3.64 (m, 1H), 3.8-3.85 (m, 1H), 3.88 (s, 3H), 5.6-5.62 (m, 1H), 7.52 (dd, J=8.2, 1.7, 1H), 7.59 (d, J=8.4, 1H), 7.76 (d, J=2.0, 1H); LRMS (FAB+) m/z (rel. intensity) 316.9 (30, [C13H1581BrO4+H]), 314.9 (47, [C13H1579BrO4+H]; LC-MS (APCI+):tR=1.48 min, m/z 334.13 (C13H1581BrO4+H3O+), 332.11 (C13H1579BrO4+H3O+); HPLC: tR=3.21 min (98%); HRMS (FAB+) Found 317.02290; C13H1681BrO4 requires 317.02115.

Workup

  1. customThe title compound was prepared
  2. customquenched with saturated NaHCO3 solution (50 mL)
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe pale yellow residue was purified by flash column chromatography [SiO2, Et2O/n-hexane (4:6)]
  7. customaffording a colourless oil
  8. customon standing at room temperature

Sources & evidence

ORD record
ord-3cf3969f6612445f939ea33d45dd3a37
Source dataset
uspto-grants-2012_04
Patent number
US08148415B2

Linked notes

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