Acetone → 3-Dibenzylamino-2,6-difluoro-benzoic acid benzyl ester

HRID 38103

Reaction equation

HRID 38103 reaction equation
[CH2:1]([N:8]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[F:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)=O.C([Li])CCC.Cl[C:34]([O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35]>O1CCCC1.O>[CH2:37]([O:36][C:34](=[O:35])[C:11]1[C:12]([F:15])=[CH:13][CH:14]=[C:9]([N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:10]=1[F:16])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

7

Reactant 4

HCID 180AcetoneHCID 10387Benzyl chloroformateHCID 58086650Dibenzyl-(2,4-difluoro-phenyl)-amineHCID 178418339Butyllithium

Product 1

HCID 584771183-Dibenzylamino-2,6-difluoro-benzoic acid benzyl esterYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To dibenzyl-(2,4-difluoro-phenyl)-amine (3.097 g, 10.02 mmol) in tetrahydrofuran (45 mL), under nitrogen atmosphere, cooled at −78° C. acetone/dry in ice bath, n-butyllithium (1.6 M in hexane, 6.88 mL, 11.02 mmol) was added slowly. The reaction was stirred for 1 hour, benzyl chloroformate (1.54 mL, 11.02 mmol) was added and the reaction was allowed to warm to room temperature during 2 hours. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 5% ethyl acetate in hexane grading to 10% acetate to provide the title compound as colourless oil (4.0 g, 90%).

Workup

  1. customdry in ice bath
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. custompurified by silica gel column chromatography
  8. washeluting with 5% ethyl acetate in hexane grading to 10% acetate

Sources & evidence

ORD record
ord-017853bc57484144b02dcfab4738d4c4
Source dataset
uspto-grants-2013_09
Patent number
US08524707B2

Linked notes

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