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

HRID 2263401Notes

Reaction equation

HRID 2263401 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][OH:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].F[C:32]1[CH:39]=[CH:38][C:35]([C:36]#[N:37])=[C:34]([O:40][CH3:41])[CH:33]=1.CCCCCCC.C(OC(C)C)(C)C>CN(C)C=O>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]=[C:14]([C:19]2[CH:20]=[CH:21][C:22]([C:25]([F:27])([F:26])[F:28])=[CH:23][CH:24]=2)[S:15][C:16]=1[CH2:17][O:18][C:32]1[CH:39]=[CH:38][C:35]([C:36]#[N:37])=[C:34]([O:40][CH3:41])[CH:33]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 27833294-Fluoro-2-methoxybenzonitrileHCID 22997467HCID 22997467, compoundHCID 59296181[4-(3-Benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-methanol

Product 1

HCID 595946624-[4-(3-Benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-benzonitrileYield 71.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1.34 g of [4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-methanol in 20 mL of dimethylformamide at 0° C. was added 158 mg of a 60% suspension of sodium hydride in mineral oil. The resulting mixture was stirred for 10 minutes at 0° C. then 497 mg of 4-fluoro-2-methoxybenzonitrile were added. After stirring for 30 minutes at 0° C., the temperature was allowed to warm up to room temperature and the reaction mixture was stirred until completion. The solvent was removed under reduced pressure and dichloromethane/water were added to the residue. The organic layer was separated and the aqueous layer extracted three times with dichloromethane. The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give 1.82 g of crude product as a yellow oil. A 1/1 solution of heptane/diisopropyl ether was added to the residue and the solidified product was filtered off to provide a first crop of 1.26 g of desired product. The mother liquor was concentrated and purified by column chromatography on silica gel (heptane 60/ethyl acetate 40) to give an additional 110 mg. The two fractions were combined to obtain 1.37 g of 4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-benzonitrile.

Workup

  1. stirringAfter stirring for 30 minutes at 0° C.
  2. temperatureto warm up to room temperature
  3. stirringthe reaction mixture was stirred until completion
  4. customThe solvent was removed under reduced pressure and dichloromethane/water
  5. additionwere added to the residue
  6. customThe organic layer was separated
  7. extractionthe aqueous layer extracted three times with dichloromethane
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto give 1.82 g of crude product as a yellow oil
  13. filtrationthe solidified product was filtered off

Sources & evidence

ORD record
ord-f8ffb9c51cf646c293d202e9734c4a71
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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