Trifluoroacetic acid → HCID 18444743, compound

HRID 58181Notes

Reaction equation

HRID 58181 reaction equation
[Cl:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][C:8]([O:13][CH3:14])=[C:7]([F:15])[C:3]=1C(O)=O.C([N:18](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(O)(C(F)(F)F)=O>C(O)(C)(C)C.ClCCl>[Cl:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][C:8]([O:13][CH3:14])=[C:7]([F:15])[C:3]=1[NH2:18]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 18444740HCID 18444740, compound

Product 1

HCID 18444743HCID 18444743, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
82 °C

Procedure

A suspension of 2-chloro-6-fluoro-3,5-dimethoxybenzoic acid (10.8 g, 0.0077 mol) and triethyl amine (0.934 g, 0.0092 mol) in tert-BuOH (50 mL) was stirred for 5 min. To the resulting reaction mixture, Diphenyl phosphoryl azide (2.53 g, 0.0092 mol) was added and heated up to 82° C. and kept at this temperature for overnight. The reaction mixture was then concentrated in vacuo to obtain a crude residue. The crude residue was dissolved in dichloromethane (20 mL) and cooled to 0° C. TFA (4 mL) was added to the reaction mixture and the resultant reaction mixture was then stirred at room temperature for 2 h. The solvents were removed under vacuum and the crude residue was diluted with ethyl acetate and saturated sodium carbonate solution. The aqueous layer was separated and extracted with ethyl acetate (3×30 mL). The organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography using the eluent (gradient hexane to hexane-ether (65:35)) to afford the title compound (0.95 g, yield: 60%) as solid. MS (ESI): 205.7 [M+H]+.

Workup

  1. additionwas added
  2. waitkept at this temperature for overnight
  3. concentrationThe reaction mixture was then concentrated in vacuo
  4. customto obtain a crude residue
  5. temperaturecooled to 0° C
  6. customthe resultant reaction mixture
  7. stirringwas then stirred at room temperature for 2 h
  8. customThe solvents were removed under vacuum
  9. additionthe crude residue was diluted with ethyl acetate and saturated sodium carbonate solution
  10. customThe aqueous layer was separated
  11. extractionextracted with ethyl acetate (3×30 mL)
  12. washThe organic phase was washed with brine
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-4c7a4f0d6b5d49908c2bcdfda88622c5
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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