Sodium hydride → 2-[4-(2-Bromo-5-fluorophenoxy)piperidin-1-yl]-5-ethynylpyrimidine

HRID 729478Notes

Reaction equation

HRID 729478 reaction equation
[Br:1][C:2]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[N:16]=[CH:15][C:14]([C:17]#[C:18]C(C)(O)C)=[CH:13][N:12]=2)[CH2:7][CH2:6]1.[H-].[Na+]>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[N:12]=[CH:13][C:14]([C:17]#[CH:18])=[CH:15][N:16]=2)[CH2:7][CH2:6]1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 68818392HCID 68818392, compound

Product 1

HCID 866218082-[4-(2-Bromo-5-fluorophenoxy)piperidin-1-yl]-5-ethynylpyrimidine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

Into a 50-mL round-bottom flask equipped with a magnetic stirbar was added 4-{2-[4-(2-Bromo 5-fluorophenoxy)piperidin-1-yl]pyrimidin-5-yl}-2-methylbut-3-yn-2-ol (300 mg, 0.69 mmol) and toluene (10 mL). The reaction mixture was treated with sodium hydride (3 mg, 0.07 mmol, 60 wt % in mineral oil) and the contents of the flask heated to 110° C. without attaching a reflux condenser in order to remove the acetone formed during the deprotection stage. After 2.5 h, complete conversion of starting material was observed by TLC analysis. The reaction mixture was cooled to room temperature and then quenched with dropwise addition of a saturated aqueous NH4Cl solution (10 mL). The mixture was poured into a 125-mL separatory funnel containing water (50 mL) and the mixture was extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and the solvent was evaporated under reduced pressure. Purification by column chromatography through silica gel, eluting with 0% EtOAc in hexanes to 20% EtOAc in hexanes as a gradient gave the desired product as a clear oil.

Workup

  1. customInto a 50-mL round-bottom flask equipped with a magnetic stirbar
  2. customto remove the acetone
  3. customformed during the deprotection stage
  4. temperatureThe reaction mixture was cooled to room temperature
  5. customquenched with dropwise addition of a saturated aqueous NH4Cl solution (10 mL)
  6. additionThe mixture was poured into a 125-mL separatory funnel
  7. additioncontaining water (50 mL)
  8. extractionthe mixture was extracted with ethyl acetate (3×30 mL)
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. customthe solvent was evaporated under reduced pressure
  13. customPurification by column chromatography through silica gel
  14. washeluting with 0% EtOAc in hexanes to 20% EtOAc in hexanes as a gradient

Sources & evidence

ORD record
ord-4a92caf3dd4c4ef4a94b07ede0aa1eb0
Source dataset
uspto-grants-2009_09
Patent number
US07582633B2

Reaction notes

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