Trifluoroacetic acid → HCID 89544538, compound

HRID 2283417Notes

Reaction equation

HRID 2283417 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:11]C(=O)OC(C)(C)C)[CH2:9][CH3:10])=[C:4]([F:19])[C:3]=1[C:20]([C:22]1[CH:23]=[N:24][C:25]([NH:28]CC2C=CC(OC)=CC=2)=[CH:26][CH:27]=1)=[O:21].FC(F)(F)C(O)=O>ClCCl>[NH2:11][C@@H:8]([C:5]1[C:4]([F:19])=[C:3]([C:2]([Cl:1])=[CH:7][CH:6]=1)[C:20]([C:22]1[CH:27]=[CH:26][C:25]([NH2:28])=[N:24][CH:23]=1)=[O:21])[CH2:9][CH3:10]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 117875127HCID 117875127, compound

Product 1

HCID 89544538HCID 89544538, compoundYield 84.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

Step 8—To a solution of the tert-butyl N-[(1R)-1-[4-chloro-2-fluoro-3-(6-{[(4-methoxyphenyl)methyl]-amino}pyridine-3-carbonyl)phenyl]propyl]carbamate (109 g) in dichloromethane (2 vol) was carefully added trifluoroacetic acid (1 vol) at room temperature. The dichloromethane was removed under vacuum, additional trifluoroacetic acid (2 vol) was added and the mixture was stirred for 10 minutes before increasing the temperature to 70° C. and stirring overnight. The mixture was allowed to cool then poured slowly into a stirred mix of TBME (15 vol) and water (15 vol). The phases were separated and the remaining emulsion was filtered through GFA paper. The TBME layer was extracted into 2M HCl (2×3 vol) and the combined acidic extracts were basified (˜pH 12) and extracted with TBME (5×5 vol). The combined organic liquors were dried (Na2SO4) and concentrated to produce an oil/foam. The material was triturated with EtOAc to give 5-{3-[(1R)-1-aminopropyl]-6-chloro-2-fluorobenzoyl}pyridin-2-amine as a fine yellow powder 53.5 g, 84%. (Data for this compound are in Example 1).

Workup

  1. customat room temperature
  2. customThe dichloromethane was removed under vacuum, additional trifluoroacetic acid (2 vol)
  3. additionwas added
  4. stirringstirring overnight
  5. temperatureto cool
  6. additionthen poured slowly into a stirred
  7. additionmix of TBME (15 vol) and water (15 vol)
  8. customThe phases were separated
  9. filtrationthe remaining emulsion was filtered through GFA paper
  10. extractionThe TBME layer was extracted into 2M HCl (2×3 vol)
  11. extractionextracted with TBME (5×5 vol)
  12. dry with materialThe combined organic liquors were dried (Na2SO4)
  13. concentrationconcentrated
  14. customto produce an oil/foam
  15. customThe material was triturated with EtOAc

Sources & evidence

ORD record
ord-c25aa1bce2334a75af5a96675e62f4a6
Source dataset
uspto-grants-2015_09
Patent number
US09145354B2

Reaction notes

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