Hydrochloric Acid → (4-{[[2-(4-Fluorophenyl)ethyl](4-isopropyl-1,3-thiazol-2-yl)amino]methyl}phenyl)methanol

HRID 732173Notes

Reaction equation

HRID 732173 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH:10][C:11]2[S:12][CH:13]=[C:14]([CH:16]([CH3:18])[CH3:17])[N:15]=2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:22][C:23]1[CH:32]=[CH:31][C:26]([C:27](OC)=[O:28])=[CH:25][CH:24]=1.Cl.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.O.O.O.O.O.O.O.O.O.[O-]S([O-])(=O)=O.[Na+].[Na+]>O1CCCC1.CN(C)C=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]([CH2:22][C:23]2[CH:32]=[CH:31][C:26]([CH2:27][OH:28])=[CH:25][CH:24]=2)[C:11]2[S:12][CH:13]=[C:14]([CH:16]([CH3:18])[CH3:17])[N:15]=2)=[CH:4][CH:3]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 62649Sodium sulfate decahydrateHCID 256687Methyl 4-(bromomethyl)benzoateHCID 21226445Aluminium lithium hydrideHCID 23143316N-[2-(4-fluorophenyl)ethyl]-4-isopropyl-1,3-thiazole-2-amine

Product 1

HCID 23143244(4-{[[2-(4-Fluorophenyl)ethyl](4-isopropyl-1,3-thiazol-2-yl)amino]methyl}phenyl)methanolYield 90%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of N-[2-(4-fluorophenyl)ethyl]-4-isopropyl-1,3-thiazole-2-amine (550 mg), sodium hydride (80 mg) and N,N-dimethylformamide (5 mL) was stirred at room temperature for 1 hr. Methyl 4-(bromomethyl)benzoate (500 mg) was added to the reaction mixture under ice-cooling, and the mixture was allowed to warm to room temperature and further stirred for 1 hr. The reaction mixture was poured into 1N hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:9-1:1 in volume ratio) to give a yellow oil. The yellow oil was dissolved in tetrahydrofuran (30 mL) and lithium aluminum hydride (80 mg) was added by small portions under ice-cooling. The reaction mixture was stirred under ice-cooling for 30 min and sodium sulfate 10 hydrate (1.0 g) was added. The mixture was allowed to warm to room temperature and stirred for 30 min. The resulting precipitate was filtered off and the filtrate was concentrated to give the title compound (720 mg, yield 90%) as a yellow oil.

Workup

  1. temperaturecooling
  2. temperatureto warm to room temperature
  3. stirringfurther stirred for 1 hr
  4. extractionextracted with ethyl acetate
  5. dry with materialThe ethyl acetate layer was dried over anhydrous magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:9-1:1 in volume ratio)
  8. customto give a yellow oil
  9. temperaturecooling
  10. stirringThe reaction mixture was stirred under ice-
  11. temperaturecooling for 30 min
  12. temperatureto warm to room temperature
  13. stirringstirred for 30 min
  14. filtrationThe resulting precipitate was filtered off
  15. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-7cea4a891d1941f1af6eb0ce9a7c6151
Source dataset
uspto-grants-2009_09
Patent number
US07585880B2

Reaction notes

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