Triethylamine → 2-[2-[4-[(5-Methyl-2-phenyl-4-thiazolyl)methoxy]benzyloxy]-3-pyridyl]acetonitrile

HRID 1294177Notes

Reaction equation

HRID 1294177 reaction equation
[CH3:1][C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:30]=[CH:29][C:18]([CH2:19][O:20][C:21]2[C:26]([CH2:27]O)=[CH:25][CH:24]=[CH:23][N:22]=2)=[CH:17][CH:16]=1.[CH2:31]([N:33](CC)CC)C.CS(Cl)(=O)=O.[C-]#N.[Na+]>O.CS(C)=O.C(OCC)(=O)C>[CH3:1][C:2]1[S:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([CH2:19][O:20][C:21]2[C:26]([CH2:27][C:31]#[N:33])=[CH:25][CH:24]=[CH:23][N:22]=2)=[CH:29][CH:30]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 8929Sodium CyanideHCID 31297Methanesulfonyl chlorideHCID 68884317[2-[4-[(5-Methyl-2-phenyl-4-thiazolyl)methoxy]benzyloxy]-3-pyridyl]methanol

Product 1

HCID 688870842-[2-[4-[(5-Methyl-2-phenyl-4-thiazolyl)methoxy]benzyloxy]-3-pyridyl]acetonitrileYield 68.5%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of [2-[4-[(5-methyl-2-phenyl-4-thiazolyl)methoxy]benzyloxy]-3-pyridyl]methanol (2.00 g), triethylamine (0.97 g) and ethyl acetate (150 mL) was dropwise added methanesulfonyl chloride (1.10 g) under ice-cooling and the mixture was stirred at room temperature for 2 hrs. The reaction mixture was washed successively with water, saturated aqueous sodium hydrogencarbonate and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give an oil. To a mixture of this oil and dimethyl sulfoxide (30 mL) was added an aqueous solution (3 mL) of sodium cyanide (0.59 g) at room temperature and the mixture was stirred at room temperature for 3 hrs. Water was added to the reaction mixture, and the precipitated crystals were collected by filtration. The obtained crystals were subjected to silica gel column chromatography to give crystals (1.40 g, 68%) of 2-[2-[4-[(5-methyl-2-phenyl-4-thiazolyl)methoxy]benzyloxy]-3-pyridyl]acetonitrile from a fraction eluted with ethyl acetate-hexane (1:2, v/v). Recrystallization from tetrahydrofuran-hexane gave colorless prism crystals. melting point: 161-162° C.

Workup

  1. temperaturecooling
  2. washThe reaction mixture was washed successively with water, saturated aqueous sodium hydrogencarbonate and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customto give an oil
  6. stirringthe mixture was stirred at room temperature for 3 hrs
  7. filtrationthe precipitated crystals were collected by filtration

Sources & evidence

ORD record
ord-a86eadcf5e4c4bb8951c9c790f9e820f
Source dataset
uspto-grants-2007_07
Patent number
US07238716B2

Reaction notes

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