Phenacyl bromide → (4-([(4-Phenyl-1,3-thiazol-2-yl)(2-pyridin-2-ylethyl)amino]methyl}phenyl)methanol

HRID 732172Notes

Reaction equation

HRID 732172 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=O.[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH2:17][CH2:18][NH:19][C:20]([NH2:22])=[S:21].[H-].[Na+].Br[CH2:26][C:27]1[CH:36]=[CH:35][C:30]([C:31]([O:33]C)=O)=[CH:29][CH:28]=1.P([O-])(O)(O)=O.[Na+].[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>[C:5]1([C:3]2[N:22]=[C:20]([N:19]([CH2:26][C:27]3[CH:28]=[CH:29][C:30]([CH2:31][OH:33])=[CH:35][CH:36]=3)[CH2:18][CH2:17][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][N:11]=3)[S:21][CH:2]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

10

Reactant 7

HCID 6259Phenacyl bromideHCID 24758Sodium hydrideHCID 62649Sodium sulfate decahydrateHCID 256687Methyl 4-(bromomethyl)benzoateHCID 21226445Aluminium lithium hydrideHCID 23143296[2-(Pyridin-2-yl)ethyl]thioureaHCID 23672064Monosodium phosphate

Product 1

HCID 23143295(4-([(4-Phenyl-1,3-thiazol-2-yl)(2-pyridin-2-ylethyl)amino]methyl}phenyl)methanolYield 44.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-bromo-1-phenylethanone (1.0 g), N-(2-pyridin-2-ylethyl)thiourea (0.90 g) and N,N-dimethylformamide (5 mL) was stirred at room temperature for 1 hr. Sodium hydride (60% in oil, 400 mg) was added to the reaction mixture and the mixture was further stirred at room temperature for 1 hr. Methyl 4-(bromomethyl)benzoate (1.15 g) 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 aqueous sodium dihydrogenphosphate solution 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=1:9-2:1 in volume ratio) to give a yellow oil. The yellow oil was dissolved in tetrahydrofuran (30 mL) and lithium aluminum hydride (120 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 (890 mg, yield 44%) as a yellow oil.

Workup

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

Sources & evidence

ORD record
ord-98cbd4702c734d18be6bb945dec5ae1e
Source dataset
uspto-grants-2009_09
Patent number
US07585880B2

Reaction notes

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