3,4-dihydro-2H-pyran → 2-(4-bromo-3-fluoro-5-((tetrahydro-2H-pyran-2-yloxy)methyl)phenoxy)tetrahydro-2H-pyran

HRID 1020795Notes

Reaction equation

HRID 1020795 reaction equation
[Br:1][C:2]1[C:7]([CH2:8][OH:9])=[CH:6][C:5]([OH:10])=[CH:4][C:3]=1[F:11].[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1>ClCCl.CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O>[Br:1][C:2]1[C:7]([CH2:8][O:9][CH:13]2[CH2:14][CH2:15][CH2:16][CH2:17][O:12]2)=[CH:6][C:5]([O:10][CH:17]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:4][C:3]=1[F:11]

Participants

5

Reactant 2

HCID 80803,4-dihydro-2H-pyranHCID 667266582-Bromo-3-fluoro-5-hydroxybenzyl alcohol

Product 1

HCID 667261942-(4-bromo-3-fluoro-5-((tetrahydro-2H-pyran-2-yloxy)methyl)phenoxy)tetrahydro-2H-pyranYield 92.1%

Reagents, catalysts & solvents 2

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-CatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-bromo-3-fluoro-5-(hydroxymethyl)phenol (5.64 g, 25.5 mmol), 3,4-dihydro-2H-pyran (5.8 mL, 64 mmol), and dl-camphorsulfonic acid (118 mg, 2 mol %) in dichloromethane (150 mL) was stirred at room temperature for overnight. The mixture was washed with saturated aqueous sodium bicarbonate and brine, and dried on anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by silica gel chromatography (9:1 hexane/ethyl acetate) to give 2-(4-bromo-3-fluoro-5-((tetrahydro-2H-pyran-2-yloxy)methyl)phenoxy)tetrahydro-2H-pyran (9.14 g, 92%).

Workup

  1. washThe mixture was washed with saturated aqueous sodium bicarbonate and brine
  2. dry with materialdried on anhydrous sodium sulfate
  3. customThe solvent was removed in vacuo
  4. customthe residue was purified by silica gel chromatography (9:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-e0016dcd3b804ad5947d97beee685d82
Source dataset
uspto-grants-2014_05
Patent number
US08716478B2

Reaction notes

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