Pyridine → (2,4-Difluoro-phenyl)-carbamic acid methyl ester

HRID 60079Notes

Reaction equation

HRID 60079 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH2:9].N1C=CC=CC=1.Cl[C:17]([O:19][CH3:20])=[O:18]>ClCCl>[CH3:20][O:19][C:17](=[O:18])[NH:9][C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[F:1]

Participants

5

Reactant 3

HCID 1049PyridineHCID 6586Methyl chloroformateHCID 97092,4-Difluoroaniline

Product 1

HCID 4674510(2,4-Difluoro-phenyl)-carbamic acid methyl esterYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Into a reaction flask under nitrogen, 2,4-difluoro-phenylamine (1, 50.00 g, 390 mmol) is combined with 550 mL of anhydrous dichloromethane and anhydrous pyridine (61.27 g, 770 mmol). Methyl chloroformate (43.92 g, 460 mmol) is added dropwise while cooling to maintain the temperature in the range of 20-30° C. The reaction is stirred overnight, then concentrated under vacuum. The resulting material is diluted with 250 mL of water, adjusted to pH 2 with 2M hydrochloric acid, and extracted with 3×250 mL of ethyl acetate. The organic layers are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is slurried from hexane and the resulting solid is collected by filtration and dried to provide the desired compound (2, 71.06 g, 98%).

Workup

  1. temperaturewhile cooling
  2. concentrationconcentrated under vacuum
  3. additionThe resulting material is diluted with 250 mL of water
  4. extractionextracted with 3×250 mL of ethyl acetate
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under vacuum
  8. filtrationthe resulting solid is collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-3b482052809f4255ab1a1cf3efbde2ea
Source dataset
uspto-grants-2016_09
Patent number
US09440969B2

Reaction notes

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