Hydrochloric Acid → (2,4-Difluoro-3-formyl-phenyl)-carbamic acid tert-butyl ester

HRID 1247418Notes

Reaction equation

HRID 1247418 reaction equation
[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=1[F:15])([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.CN([CH:25]=[O:26])C.Cl>C1COCC1.CCOC(C)=O.O>[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[C:10]([CH:25]=[O:26])[C:9]=1[F:15])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 22986665Tert-butyl (2,4-difluorophenyl)carbamateHCID 178418339Butyllithium

Product 1

HCID 58086596(2,4-Difluoro-3-formyl-phenyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred, cooled (−78° C.) solution of (2,4-difluoro-phenyl)-carbamic acid tert-butyl ester (5 g) in THF (50 ml) under an argon atmosphere was added dropwise a 1.6 M solution of BuLi in hexanes (28.6 ml) for 20 min (temperature below −68° C. during the addition). When addition was complete, the mixture (turning to orange, then to light red) was stirred at −78° C. for 1 h 30. DMF (7.55 ml) was then added for 10 min (temperature below −70° C.) and stirring at −78° C. was continued for 15 min. As the mixture had turned to a compact mas (no more stirring), it was allowed to warm to room temperature. Water (50 ml) was added and the pH was set to 3 by the dropwise addition of 3 N HCl. EtOAc (50 ml) was added. The organic phase was washed with water and brine dried over MgSO4, filtered and concentrated. The crude product was purified by flash chromatography (cyclohexane=>cyclohexane/EtOAc 85:15) to give (2,4-difluoro-3-formyl-phenyl)-carbamic acid tert-butyl ester (1.75 g) as an off-white solid.

Workup

  1. additionduring the addition)
  2. additionWhen addition
  3. stirringstirring at −78° C.
  4. waitwas continued for 15 min
  5. stirringno more stirring), it
  6. temperatureto warm to room temperature
  7. washThe organic phase was washed with water and brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by flash chromatography (cyclohexane=>cyclohexane/EtOAc 85:15)

Sources & evidence

ORD record
ord-4101edea20884581b66eb06029555da1
Source dataset
uspto-grants-2006_10
Patent number
US07129238B2

Reaction notes

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