Sodium hydride → 4-[4-(3-Benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-benzonitrile

HRID 2263441Notes

Reaction equation

HRID 2263441 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]=[C:14]([C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=2)[S:15][C:16]=1[CH2:17]Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[F:31][C:32]1[CH:39]=[C:38]([OH:40])[CH:37]=[CH:36][C:33]=1[C:34]#[N:35]>CN(C=O)C>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]=[C:14]([C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=2)[S:15][C:16]=1[CH2:17][O:40][C:38]1[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[C:32]([F:31])[CH:39]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27346752-Fluoro-4-hydroxybenzonitrileHCID 595946804-(3-Benzyloxy-propyl)-5-chloromethyl-2-(4-trifluoromethyl-phenyl)-thiazole

Product 1

HCID 595946854-[4-(3-Benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-benzonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 0.82 g of 4-(3-benzyloxy-propyl)-5-chloromethyl-2-(4-trifluoromethyl-phenyl)-thiazole in 12 mL of DMF at 0° C. was added 0.1 g NaH 55%. The reaction mixture was stirred at 0° C. for 10 min then 2-0.264 g of fluoro-4-hydroxybenzonitrile was added at this temperature. The reaction mixture was stirred at 0° C. for 1 h30, allowed to warm up to room temperature and then stirred for 4 h at room temperature. The solvent was removed and the resulting residue was taken up into dichloromethane then water was added. After decantation and separation, the aqueous layer was extracted three times with dichloromethane. The combined organic layers were washed with water, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 0.91 g of crude product as a yellow oil. Purification by column chromatography on silica gel (heptane 1/ether 1) gave 840 mg of 4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-benzonitrile as a white foam.

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 1 h30
  2. temperatureto warm up to room temperature
  3. stirringstirred for 4 h at room temperature
  4. customThe solvent was removed
  5. additionwater was added
  6. customAfter decantation and separation
  7. extractionthe aqueous layer was extracted three times with dichloromethane
  8. washThe combined organic layers were washed with water
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto give 0.91 g of crude product as a yellow oil
  13. customPurification by column chromatography on silica gel (heptane 1/ether 1)

Sources & evidence

ORD record
ord-b0285968ffdc43498cf40a0b20f4623f
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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