Triethylamine → HCID 22632966, compound

HRID 2270242Notes

Reaction equation

HRID 2270242 reaction equation
[CH:1]1([NH:4][C:5]2[C:13]([F:14])=[C:12]([N:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[C:11]([F:20])=[CH:10][C:6]=2[C:7]([OH:9])=O)[CH2:3][CH2:2]1.[C:21]([N:28]1C=CN=C1)(N1C=CN=C1)=[O:22].C(N(CC)CC)C.Cl.[C:41]([O:45]N)([CH3:44])([CH3:43])[CH3:42]>C1COCC1.O>[C:41]([O:45][N:28]1[C:7](=[O:9])[C:6]2[C:5](=[C:13]([F:14])[C:12]([N:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)=[C:11]([F:20])[CH:10]=2)[N:4]([CH:1]2[CH2:2][CH2:3]2)[C:21]1=[O:22])([CH3:44])([CH3:43])[CH3:42]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-Carbonyldiimidazole2×HCID 2777906O-tert-butylhydroxylamine hydrochlorideHCID 22633013HCID 22633013, compound

Product 1

HCID 22632966HCID 22632966, compoundYield 23.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-cyclopropylamino-3,5-difluoro-4-pyrrolidin-1-yl-benzoic acid (Example T-3, 1.65 g, 5.85 mmol) in THF (20 mL) was reacted with carbonyldiimidazole (1.2 g, 7.31 mmol) and stirred overnight at ambient temperature. The mixture was reacted with triethylamine (1.22 mL, 8.77 mmol) and O-t-butyl hydroxylamine hydrochloride (1.10 g, 8.77 mmol) and allowed to stir for 4 hours. The mixture was quenched with H2O and extracted with ethyl acetate. The organic layers were combined, dried with sodium sulfate, and concentrated. The resulting residue was dissolved in THF (15 mL), reacted with carbonyldiimidazole (2.44 g, 15.0 mmol), and heated to 100° C. in a sealed tube for 5 days. The mixture was cooled, diluted with H2O, and extracted with ethyl acetate. The organic layer was washed with H2O, dried with sodium sulfate, and concentrated. The residue was purified by column chromatography (silica gel, 1:1 hexanes/ethyl acetate) to provide 0.52 g of the title compound as a solid.

Workup

  1. stirringto stir for 4 hours
  2. customThe mixture was quenched with H2O
  3. extractionextracted with ethyl acetate
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated
  6. dissolutionThe resulting residue was dissolved in THF (15 mL)
  7. temperatureheated to 100° C. in a sealed tube for 5 days
  8. temperatureThe mixture was cooled
  9. extractionextracted with ethyl acetate
  10. washThe organic layer was washed with H2O
  11. dry with materialdried with sodium sulfate
  12. concentrationconcentrated
  13. customThe residue was purified by column chromatography (silica gel, 1:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-cbcd3e2a35804d6c8e29dfd57a25b244
Source dataset
uspto-grants-2001_12
Patent number
US06331538B1

Reaction notes

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