Ethyl Acetate → [(3R)-3-(5-Chloro-2-cyanophenoxy)-3-(2-thiazolyl)propyl]carbamic acid 1,1-dimethylethyl ester

HRID 2179952Notes

Reaction equation

HRID 2179952 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4](F)[CH:3]=1.[CH3:11][C:12]([O:15][C:16](=[O:27])[NH:17][CH2:18][CH2:19][C@@H:20]([OH:26])[C:21]1[S:22][CH:23]=[CH:24][N:25]=1)([CH3:14])[CH3:13].[H-].[Na+].C(OCC)(=O)C>CN(C)C=O.CCCC(C)C>[CH3:14][C:12]([O:15][C:16](=[O:27])[NH:17][CH2:18][CH2:19][C@@H:20]([O:26][C:4]1[CH:3]=[C:2]([Cl:1])[CH:9]=[CH:8][C:5]=1[C:6]#[N:7])[C:21]1[S:22][CH:23]=[CH:24][N:25]=1)([CH3:11])[CH3:13]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 936554-Chloro-2-fluorobenzonitrileHCID 69803796[(3R)-3-Hydroxy-3-(2-thiazolyl)propyl]carbamic acid 1,1-dimethylethyl ester

Product 1

HCID 69804096[(3R)-3-(5-Chloro-2-cyanophenoxy)-3-(2-thiazolyl)propyl]carbamic acid 1,1-dimethylethyl esterYield 87.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 78922-MethylpentaneSolvent

Procedure

To a solution of 4-chloro-2-fluorobenzonitrile (156 mg, 1 mmol) and [(3R)-3-hydroxy-3-(2-thiazolyl)propyl]carbamic acid 1,1-dimethylethyl ester (258 mg, 1 mmol) in dry dimethylformamide (3 ml), was added sodium hydride (60% dispersion in oil, 40 mg, 1 mmol) and the mixture was stirred at room temperature for 16 h. The reaction was quenched with methanol 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, 15% ethyl acetate in isohexane) gave 345 mg of a white solid (86%).

Workup

  1. customThe reaction was quenched with methanol
  2. custompartitioned between ethyl acetate and water
  3. washThe combined extracts were washed with water (3×25 ml) and saturated brine solution
  4. dry with materialdried (magnesium sulphate)
  5. concentrationconcentrated in vacuo
  6. customto leave a crude yellow gum

Sources & evidence

ORD record
ord-afc88fd3788c424bb1f9305052a214b0
Source dataset
uspto-grants-2005_05
Patent number
US06887871B2

Reaction notes

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