Triethylamine → Ethyl 2-[6-azido-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetate

HRID 246950Notes

Reaction equation

HRID 246950 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:23]=[C:22](O)[C:21]([F:25])=[CH:20][C:11]=1[C:12]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:13].C(N(CC)CC)C.C1(P([N:47]=[N+:48]=[N-:49])(C2C=CC=CC=2)=O)C=CC=CC=1.C(OCC)(=O)C>C(#N)C.O>[N:47]([C:22]1[C:21]([F:25])=[CH:20][C:11]([C:12]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:13])=[C:10]([NH:9][C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])[N:23]=1)=[N+:48]=[N-:49]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 199401P,P-Diphenylphosphinic azideHCID 178472175Ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-hydroxynicotinoyl]acetate

Product 1

HCID 13849326Ethyl 2-[6-azido-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetateYield 48.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

In 10 ml of anhydrous acetonitrile was suspended 1.05 g of ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-hydroxynicotinoyl]acetate, and 450 mg of triethylamine and 1.22 g of diphenylphosphoryl azide were added thereto with ice-cooling, after which the resulting mixture was subjected to reaction at room temperature for 4 hours. To this reaction mixture were added 50 ml of ethyl acetate and 50 ml of water, and the organic layer was separated, and then dried over anhydrous magnesium sulfate. The solvent was removed by ditillation under reduced pressure, and the residue thus obtained was purified by a column chromoatography [Wako Silica Gel C-200, eluant: benzene] to obtain 550 mg (yield 48.9%) of ethyl 2-[6-azido-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetate having a melting point of 130°-131° C.

Workup

  1. additionwere added
  2. temperaturewith ice-cooling
  3. customafter which the resulting mixture was subjected to reaction at room temperature for 4 hours
  4. customthe organic layer was separated
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was removed by ditillation under reduced pressure
  7. customthe residue thus obtained
  8. customwas purified by a column chromoatography [Wako Silica Gel C-200, eluant: benzene]

Sources & evidence

ORD record
ord-9ffbecff335942f39850fb7287b4fbed
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

Loading…