Cesium carbonate → 1-[4-(6-Chloro-pyridin-3-ylmethoxy)-2-hydroxy-3-propyl-phenyl]-ethanone

HRID 2267026Notes

Reaction equation

HRID 2267026 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([Cl:9])=[N:7][CH:8]=1.[OH:10][C:11]1[C:16]([CH2:17][CH2:18][CH3:19])=[C:15]([OH:20])[CH:14]=[CH:13][C:12]=1[C:21](=[O:23])[CH3:22].C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[Cl:9][C:6]1[N:7]=[CH:8][C:3]([CH2:2][O:20][C:15]2[CH:14]=[CH:13][C:12]([C:21](=[O:23])[CH3:22])=[C:11]([OH:10])[C:16]=2[CH2:17][CH2:18][CH3:19])=[CH:4][CH:5]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 1554792-Chloro-5-(chloromethyl)pyridineHCID 27751982',4'-Dihydroxy-3'-propylacetophenone

Product 1

HCID 866198471-[4-(6-Chloro-pyridin-3-ylmethoxy)-2-hydroxy-3-propyl-phenyl]-ethanoneYield 36.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Add 5-chloromethyl-2-chloropyridine (4.12 g, 25.4 mmol) to a solution of 1-(2,4-dihydroxy-3-propyl-phenyl)-ethanone (4.94 g, 25.4 mmol) in dimethylformamide (40 mL). After 10 minutes add potassium carbonate (5.27 g, 38.1 mmol) and cesium carbonate (8.28 g, 25.4 mmol). Stir at room temperature for one hour, and then heat to 70° C. for 2 hours. Cool, partition between ethyl acetate (300 mL) and water (300 mL). Wash twice with water, brine, dry, and concentrate. Dissolve the crude solid in dichloromethane, and add hexane (70 mL) slowly. Triturate and filter to afford the title compound as an orange powder (2.95 g, 36%): 1H NMR (CDCl3) δ 0.94 (t, 3H), 1.55 (sextet, 2H), 2.58 (s, 3H), 2.67 (t, 2H), 5.14 (s, 2H), 6.47 (d, 1H), 7.38 (d, 1H), 7.60 (d, 1H), 7.73 (d, 1H), 8.47 (s, 1H), 12.75 (s, 1H).

Workup

  1. temperatureheat to 70° C. for 2 hours
  2. temperatureCool
  3. custompartition between ethyl acetate (300 mL) and water (300 mL)
  4. washWash twice with water, brine
  5. customdry
  6. concentrationconcentrate
  7. dissolutionDissolve the crude solid in dichloromethane
  8. additionadd hexane (70 mL) slowly
  9. customTriturate
  10. filtrationfilter

Sources & evidence

ORD record
ord-e640a989466d499a828115adb400007f
Source dataset
uspto-grants-2010_12
Patent number
US07858646B2

Reaction notes

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