Methyl iodide → [(3R)-3-(5-Chloro-2-cyanophenoxy)-3-(2-thiazolyl)propyl]methylcarbamic acid 1,1-dimethylethyl ester

HRID 2179954Notes

Reaction equation

HRID 2179954 reaction equation
[CH3:1][C:2]([O:5][C:6](=[O:26])[NH:7][CH2:8][CH2:9][C@@H:10]([O:16][C:17]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=1[C:24]#[N:25])[C:11]1[S:12][CH:13]=[CH:14][N:15]=1)([CH3:4])[CH3:3].[H-].[Na+].IC.[C:31](OCC)(=O)C>O1CCCC1.CCCC(C)C>[CH3:4][C:2]([O:5][C:6](=[O:26])[N:7]([CH2:8][CH2:9][C@@H:10]([O:16][C:17]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=1[C:24]#[N:25])[C:11]1[S:12][CH:13]=[CH:14][N:15]=1)[CH3:31])([CH3:1])[CH3:3]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 69804096[(3R)-3-(5-Chloro-2-cyanophenoxy)-3-(2-thiazolyl)propyl]carbamic acid 1,1-dimethylethyl ester

Product 1

HCID 86759693[(3R)-3-(5-Chloro-2-cyanophenoxy)-3-(2-thiazolyl)propyl]methylcarbamic acid 1,1-dimethylethyl esterYield 98%

Reagents, catalysts & solvents 2

HCID 78922-MethylpentaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [(3R)-3-(5-chloro-2-cyanophenoxy)-3-(2-thiazolyl)propyl]-carbamic acid 1,1-dimethylethyl ester (200 mg, 0.51 mmol) in dry tetrahydrofuran (10 ml), was added sodium hydride (56 mg, 60% dispersion in oil, 1.41 mmol) and stirred at room temperature for 15 minutes. Iodomethane (1.325 g, 0.58 ml, 4.7 mmol) was added. The reaction was stirred at room temperature for 18 h, quenched with saturated ammonium chloride solution and partitioned between ethyl acetate and water. The combined extracts were washed with water (3×25 ml) and saturated brine solution, dried (magnesium sulphate) and concentrated in vacuo to leave a crude yellow gum. Flash chromatography (silica, 25% ethyl acetate in isohexane) afforded 175 mg of an opaque oil (98%).

Workup

  1. stirringThe reaction was stirred at room temperature for 18 h
  2. customquenched with saturated ammonium chloride solution
  3. custompartitioned between ethyl acetate and water
  4. washThe combined extracts were washed with water (3×25 ml) and saturated brine solution
  5. dry with materialdried (magnesium sulphate)
  6. concentrationconcentrated in vacuo
  7. customto leave a crude yellow gum

Sources & evidence

ORD record
ord-4cd08753bae647218941a2e9c23b509c
Source dataset
uspto-grants-2005_05
Patent number
US06887871B2

Reaction notes

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