Phenol → 2-(2-Fluoro-4-phenoxy-benzyloxy)-tetrahydro-pyran

HRID 911459Notes

Reaction equation

HRID 911459 reaction equation
Br[C:2]1[CH:15]=[CH:14][C:5]([CH2:6][O:7][CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][O:9]2)=[C:4]([F:16])[CH:3]=1.[C:17]1([OH:23])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CC(C)(C(=O)CC(=O)C(C)(C)C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu]Cl.CN1C(=O)CCC1>[F:16][C:4]1[CH:3]=[C:2]([O:23][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:15]=[CH:14][C:5]=1[CH2:6][O:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][O:9]1

Participants

7

Reactant 4

HCID 996PhenolHCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 576563392-(4-Bromo-2-fluorobenzyloxy)-tetrahydropyran

Product 1

HCID 576563912-(2-Fluoro-4-phenoxy-benzyloxy)-tetrahydro-pyranYield 68%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

Mix under argon atmosphere 2-(4-bromo-2-fluorobenzyloxy)-tetrahydropyran (2.9 g, 10 mmol), phenol (1.9 g, 20 mmol), 2,2,6,6-tetramethylheptane-3,5-dione (184.3 mg, 1.0 mmol), cesium carbonate (6.5 g, 20 mmol) and anhydrous NMP (20 mL). Degas the flask and fill with argon. Add copper(I) chloride (495 mg, 5 mmol) quickly. Degas the flask three times then fill with argon. Heat at 120° C. for 3 h. Cool to ambient temperature. Dilute with EtOAc and filter. Concentrate in vacuo and purify by chromatography on silica gel to obtain the desired intermediate (2.05 g, 68%). MS (ES+) m/z: 325 (M+Na)+.

Workup

  1. customDegas the flask
  2. customDegas the flask three times
  3. temperatureCool to ambient temperature
  4. additionDilute with EtOAc
  5. filtrationfilter
  6. concentrationConcentrate in vacuo
  7. custompurify by chromatography on silica gel

Sources & evidence

ORD record
ord-805b42ba7497497e8b021886ea4426ab
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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