Trifluoroacetic acid → 4-(5-Chloro-isoquinolin-6-yloxy)-cyclohexanone

HRID 2370736Notes

Reaction equation

HRID 2370736 reaction equation
[Cl:1][C:2]1[C:11]([O:12][CH:13]2[CH2:22][CH2:21][C:16]3(OCC[O:17]3)[CH2:15][CH2:14]2)=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.C(O)(C(F)(F)F)=O>C1COCC1.O.ClCCl.O.C([O-])(O)=O.[Na+]>[Cl:1][C:2]1[C:11]([O:12][CH:13]2[CH2:14][CH2:15][C:16](=[O:17])[CH2:21][CH2:22]2)=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2

Participants

7

Reactant 2

HCID 6422Trifluoroacetic acid4×HCID 592685835-Chloro-6-(1,4-dioxa-spiro[4.5]dec-8-yloxy)-isoquinoline

Product 1

HCID 592685134-(5-Chloro-isoquinolin-6-yloxy)-cyclohexanone

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

549 mg (1.72 mmol) 5-Chloro-6-(1,4-dioxa-spiro[4.5]dec-8-yloxy)-isoquinoline (78) were dissolved in 20 ml THF/H2O (3:1). 1 ml TFA was added and the mixture was stirred at room temperature. After 1 h, 2 ml TFA were added and the temperature was increased to 50° C. After 5 d at 50° C., 2 ml TFA were added. After one additional day, 2 ml TFA were added and the temperature was increased to 100° C. After 5 h, the reaction was allowed to cool down to room temperature and the mixture was diluted with dichloromethane and H2O, Solid NaHCO3 was added for neutralization. The phases were separated and the aqueous phase was extracted with dichloromethane. The combined organic layers were dried over MgSO4 and evaporated. After final purification by preparative HPLC, 533 mg of the title compound as trifluoroacetate were obtained. Rt=0.88 min (Method #4). Detected mass: 276.2/278.2 (M+H+).

Workup

  1. temperaturethe temperature was increased to 50° C
  2. waitAfter 5 d at 50° C.
  3. temperaturethe temperature was increased to 100° C
  4. waitAfter 5 h
  5. temperatureto cool down to room temperature
  6. additionwas added for neutralization
  7. customThe phases were separated
  8. extractionthe aqueous phase was extracted with dichloromethane
  9. dry with materialThe combined organic layers were dried over MgSO4
  10. customevaporated
  11. customAfter final purification by preparative HPLC, 533 mg of the title compound as trifluoroacetate
  12. customwere obtained

Sources & evidence

ORD record
ord-9bfe03d7e1e64b2395020c9e843376e3
Source dataset
uspto-grants-2014_04
Patent number
US08710228B2

Reaction notes

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