Methyl iodide → HCID 22485163, compound

HRID 2181031Notes

Reaction equation

HRID 2181031 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([Cl:16])[CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:19]I>CN(C)C=O>[C:1]([O:5][C:6]([N:8]([CH3:19])[C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([Cl:16])[CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 4935491Carbamic acid, (3-chloro-4-methylphenyl)-, 1,1-dimethylethyl ester

Product 1

HCID 22485163HCID 22485163, compoundYield 98.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(tert-Butoxycarbonyl)-3-chloro-4-methylaniline (60.0 g) was dissolved in N,N-dimethylformamide (300 ml) and 60% sodium hydride (10.4 g) was gradually added under ice-cooling over 10 min. The reaction mixture was stirred at room temperature for 30 min and methyl iodide (38.8 g) was added dropwise over 15 min under ice-cooling. The reaction mixture was stirred at room temperature for 2 hr and concentrated under reduced pressure. Water (500 ml) was added and the mixture was extracted with ethyl acetate (500 ml). The organic layer was washed successively with water (500 ml), saturated aqueous sodium hydrogen carbonate solution (500 ml) and saturated brine (500 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted with hexane:ethyl acetate=9:1. The objective fraction was concentrated under reduced pressure to give N-(tert-butoxycarbonyl)-3-chloro-N,4-dimethylaniline as a pale-yellow oil (62.7 g). 1H-NMR(CDCl3): 1.46(9H, s), 2.34(3H, s), 3.26(3H, s), 7.04(1H, dd, J=8, 2 Hz), 7.16(1H, d, J=8 Hz), 7.24(1H, d, J=2 Hz).

Workup

  1. temperaturecooling over 10 min
  2. temperaturecooling
  3. stirringThe reaction mixture was stirred at room temperature for 2 hr
  4. concentrationconcentrated under reduced pressure
  5. additionWater (500 ml) was added
  6. extractionthe mixture was extracted with ethyl acetate (500 ml)
  7. washThe organic layer was washed successively with water (500 ml), saturated aqueous sodium hydrogen carbonate solution (500 ml) and saturated brine (500 ml)
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. washeluted with hexane
  11. concentrationThe objective fraction was concentrated under reduced pressure

Sources & evidence

ORD record
ord-bfdba8ae271b423baf327bcb68d40991
Source dataset
uspto-grants-2005_05
Patent number
US06890934B2

Reaction notes

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