3,4-dihydro-2H-pyran → 2-(4-Bromo-2-fluorobenzyloxy)-tetrahydropyran

HRID 2041338Notes

Reaction equation

HRID 2041338 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[C:4]([F:10])[CH:3]=1.[O:11]1[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12]1>C(Cl)Cl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][O:7][CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16][O:11]2)=[C:4]([F:10])[CH:3]=1

Participants

5

Reactant 2

HCID 80803,4-dihydro-2H-pyranHCID 2734027(4-Bromo-2-fluorophenyl)methanol

Product 1

HCID 576563392-(4-Bromo-2-fluorobenzyloxy)-tetrahydropyranYield 75.4%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Mix under nitrogen atmosphere 4-bromo-2-fluorobenzyl alcohol, (4.1 g, 20 mmol), dihydropyran (2 g, 24 mmol),p-toluenesulfonic acid monohydrate (100 mg, 0.52 mmol), and anhydrous DCM (70 mL). Stir for 16 h at ambient temperature. Dilute with DCM, wash sequentially with saturated aqueous NaHCO3 then brine. Separate the organic layer, dry over Na2SO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (1:0 and 9:1) to obtain the desired intermediate as a clear oil (4.36 g, 75%). MS (ES+) m/z: 312 (M+Na)+.

Workup

  1. washwash sequentially with saturated aqueous NaHCO3
  2. customSeparate the organic layer
  3. dry with materialdry over Na2SO4
  4. concentrationconcentrate in vacuo
  5. customPurify by chromatography on silica gel eluting with hexane/EtOAc (1:0 and 9:1)

Sources & evidence

ORD record
ord-2254a6dfba544fd784cf22911d45ab45
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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