Chloroacetonitrile → HCID 13326693, compound

HRID 1905717Notes

Reaction equation

HRID 1905717 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([NH:14][C:15](=[O:20])[O:16][CH:17]([CH3:19])[CH3:18])[CH:7]=[C:8]([CH2:11][O:12][CH3:13])[C:9]=1[OH:10].Cl[CH2:22][C:23]#[N:24]>CN(C)C=O>[Cl:3][C:4]1[CH:5]=[C:6]([NH:14][C:15](=[O:20])[O:16][CH:17]([CH3:18])[CH3:19])[CH:7]=[C:8]([CH2:11][O:12][CH3:13])[C:9]=1[O:10][CH2:22][C:23]#[N:24]

Participants

5

Reactant 3

HCID 7856ChloroacetonitrileHCID 24758Sodium hydrideHCID 13387367HCID 13387367, compound

Product 1

HCID 13326693HCID 13326693, compoundYield 90.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

3-Chloro-4-hydroxy-5-methoxymethylaniline (52.8 g) and N,N-diethylaniline (42.0 g) were dissolved in ethyl acetate (300 ml). To the resultant solution was dropwise added isopropyl chloroformate (34.6 g) in 15 minutes under ice-cooling. After being allowed to stand at room temperature for 12 hours, the reaction mixture was poured into ice-water. The organic layer was washed with dilute aqueous hydrochloric acid and water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography using tolouene and ethyl acetate as the eluent to give isopropyl N-(3-chloro-4-hydroxy-5-methoxymethylphenyl)carbamate (65.6 g). Sodium hydride (9.60 g, 60% dispersion in mineral oil) was added to dimethylformamide (240 ml). To the resultant mixture was added isopropyl N-(3-chloro-4-hydroxy-5-methoxymethylphenyl)carbamate (65.6 g) under 5° C. The resulting solution was stirred for 30 minutes at a temperature of 20° C. and, to this solution was added chloroacetonitrile (19.0 g) in 5 minutes. The mixture was heated at 90° C. for 10 minutes and poured into ice-water and extracted with ethyl acetate. The extract was washed with aqueous potassium carbonate solution and water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography using toluene and ethyl acetate as the eluent to give isopropyl N-(3-chloro-4-cyanomethoxy- 5-methoxymethylphenyl)carbamate (67.5 g) in a yield of 76.8%. M.P., 58.5°-60.5° C.

Workup

  1. temperatureThe mixture was heated at 90° C. for 10 minutes
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with aqueous potassium carbonate solution and water
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-48eab31a9c3d46c49598c5750c45aeef
Source dataset
uspto-grants-1987_03
Patent number
US04647583

Reaction notes

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