Hydrochloric Acid → Benzyl (2,4-difluoro-3-formylphenyl)carbamate

HRID 1397851Notes

Reaction equation

HRID 1397851 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([O:20][C:21](=[O:31])[NH:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=1[F:30])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CN(C)[CH:34]=[O:35].Cl>O1CCCC1.O>[CH2:13]([O:20][C:21](=[O:31])[NH:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[C:25]([CH:34]=[O:35])[C:24]=1[F:30])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 11954520Benzyl (2,4-difluorophenyl)carbamateHCID 178418339Butyllithium

Product 1

HCID 58086235Benzyl (2,4-difluoro-3-formylphenyl)carbamateYield 93.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Into a round bottom flask under nitrogen, diisopropylamine (17.68 g, 174.7 mmol) and 100 mL of anhydrous tetrahydrofuran were added under nitrogen. The solution was cooled to −78° C. and n-butyllithium (1.60 M in hexane, 109.2 mL, 174.7 mmol) was added dropwise, maintaining the temperature at <−70° C., and the reaction was stirred at −78° C. for 1 hour. (2,4-difluoro-phenyl)-carbamic acid benzyl ester (24, 20.00 g, 76.0 mmol) in 100 mL of anhydrous tetrahydrofuran was added dropwise, maintaining the temperature at <−70° C., and the reaction was stirred at −78° C. for 1 hour. Anhydrous dimethylformamide (13.88 g, 190.0 mmol) was added dropwise, maintaining the temperature at <−70° C., and the reaction was stirred at −78° C. for 1 hour, then warmed to room temperature and stirred for 15 minutes. The reaction mixture was poured into 150 mL of water, acidified to pH 1 with 2 M aqueous hydrochloric acid, and extracted with 3×150 mL of ethyl acetate. The organic layers were combined and dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The residue was slurried in hexane, filtered and the solid collected and dried to provide the desired compound (25, 20.69 g, 93%).

Workup

  1. temperaturemaintaining the temperature at <−70° C.
  2. temperaturemaintaining the temperature at <−70° C.
  3. stirringthe reaction was stirred at −78° C. for 1 hour
  4. temperaturemaintaining the temperature at <−70° C.
  5. stirringthe reaction was stirred at −78° C. for 1 hour
  6. temperaturewarmed to room temperature
  7. stirringstirred for 15 minutes
  8. extractionextracted with 3×150 mL of ethyl acetate
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationthe filtrate concentrated under vacuum
  12. filtrationfiltered
  13. customthe solid collected
  14. customdried

Sources & evidence

ORD record
ord-ae64619dc3b84cdc9073b0df75aae219
Source dataset
uspto-grants-2014_12
Patent number
US08901301B2

Reaction notes

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