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

HRID 1187286Notes

Reaction equation

HRID 1187286 reaction equation
[CH2:1]([O:8][C:9](=[O:19])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=1[F:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:20]1CCC[CH2:21]1.C([Li])CCC.CN(C)C=O>O>[CH2:1]([O:8][C:9](=[O:19])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([F:17])=[C:13]([CH:21]=[O:20])[C:12]=1[F:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 11954520Benzyl (2,4-difluorophenyl)carbamateHCID 178418339Butyllithium

Product 1

HCID 58086235Benzyl (2,4-difluoro-3-formylphenyl)carbamateYield 71%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
-78 °C

Procedure

In a round bottom flask (2,4-difluoro-phenyl)-carbamic acid benzyl ester (30, 3.83 g, 14.5 mmol) is combined with 148 mL of tetrahydrofuran. The solution is chilled to −78° C. and n-butyllithium (19.1 mL, 1.60 M in hexane, 30.0 mmol) is added over 30 minutes, followed by the addition of N,N-dimethylformamide (1.12 mL, 14.5 mol). The reaction mixture is allowed to warm to ambient temperature and is stirred overnight, then poured into water and extracted with ethyl acetate. The organic layer is washed with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is crystallized from ether to provide the desired compound (33, 3.0 g, 71%).

Workup

  1. temperatureto warm to ambient temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer is washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under vacuum
  7. customThe resulting material is crystallized from ether

Sources & evidence

ORD record
ord-43c8be0d3dbb40f1a20b58d4df3a151c
Source dataset
uspto-grants-2014_03
Patent number
US08673928B2

Reaction notes

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