3,4-dihydro-2H-pyran → 1-[2-Fluoro-4-(tetrahydro-pyran-2-yloxy)-phenyl]-ethanone

HRID 30609Notes

Reaction equation

HRID 30609 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:11])[CH3:10].[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH:13]2[CH2:14][CH2:15][CH2:16][CH2:17][O:12]2)[CH:5]=[CH:4][C:3]=1[C:9](=[O:11])[CH3:10]

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 27249122'-Fluoro-4'-hydroxyacetophenone

Product 1

HCID 687437521-[2-Fluoro-4-(tetrahydro-pyran-2-yloxy)-phenyl]-ethanoneYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(2-fluoro-4-hydroxy-phenyl)-ethanone (130 mmol), 3,4-dihydro-2H-pyran (260 mmol) and a catalytic amount of pyridinium p-toluenesulfonate in CH2Cl2 (200 mL) was left overnight at room temperature. The organic phase was washed with 1 N NaOH (aq) (1×50 mL) and dried (K2CO3). Evaporation in vacuo gave a brown oil, that was purified by vacuum distillation. The desired product was isolated as clear oil in 74% yield: bp: 130-140 ° C./0.05 mbar. 1H-NMR (CDCl3) δ 7.86 (t, 1H), 6.87 (dd, 1H), 6.82 (dd, 1H), 5.49 (t, 1H), 3.86-3.78 (m, 1H), 3.67-3.61 (m, 1H), 2.59 (d, 3H), 1.97-1.60 (m, 6H).

Workup

  1. washThe organic phase was washed with 1 N NaOH (aq) (1×50 mL)
  2. dry with materialdried (K2CO3)
  3. customEvaporation in vacuo
  4. customgave a brown oil, that
  5. distillationwas purified by vacuum distillation

Sources & evidence

ORD record
ord-d0a16c2b327249bca658ff0b7de8fb06
Source dataset
uspto-grants-2008_09
Patent number
US07423181B2

Reaction notes

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