Trifluoroacetic acid → HCID 10197819, compound

HRID 1518959Notes

Reaction equation

HRID 1518959 reaction equation
C([N:8]1[CH2:13][CH2:12][CH2:11][C:10](=O)[CH2:9]1)(OC(C)(C)C)=O.[C:15]1([Mg]Br)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.FC(F)(F)C(O)=O>C1COCC1.O.CCOC(C)=O>[C:15]1([C:10]2[CH2:9][NH:8][CH2:13][CH2:12][CH:11]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylateHCID 178418255HCID 178418255, compound

Product 1

HCID 10197819HCID 10197819, compoundYield 98%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Add slowly (over 70 min) a solution of N-Boc-3-Piperidone (494.35 mmol; 98.50 mL; 98.50 g) in anhydrous THF (118.20 mL) to a suspension of 1M phenyl magnesium bromide in THF (593.22 mmol; 593.22 mL; 593.22 g) at 0° C. under nitrogen. Stir the mixture at 0° C. for 1.5 h. Then, add slowly trifluoroacetic acid (593.22 mmol; 44.86 mL). Concentrate partially the mixture removing about 450 mL of solvent to give brown oil and stir at 22° C. for 1 h. Then, add trifluoroacetic acid (9.81 moles; 741.53 mL) to this residue at 10° C. Stir the mixture at 22° C. for 15 min to give a red solution. Then, warm the red solution at 75° C. for 2 h and cool slowly to 22° C. for 18 h. Concentrate the mixture. Add an aqueous solution (50%) of NA OH (3.46 moles; 266.17 mL) to the resulting brown suspension at −20° C. Dilute the suspension with water (1 L) and EtOAc (3 L) and concentrate. Filter the brown suspension and concentrate the mother liquors to give a brown solution. Extract this solution with DCM (5×800 mL) and concentrate the organic layers. Filter the aqueous layer through CELITE® and separate the filtrates. Concentrate all the combined organics to give the title compound as brown oil (103.1 g, 98%). MS (m/z): 160 (M+1).

Workup

  1. concentrationConcentrate partially the mixture
  2. customremoving about 450 mL of solvent
  3. customto give brown oil
  4. stirringstir at 22° C. for 1 h
  5. stirringStir the mixture at 22° C. for 15 min
  6. customto give a red solution
  7. temperatureThen, warm the red solution at 75° C. for 2 h
  8. temperaturecool slowly to 22° C. for 18 h
  9. concentrationConcentrate the mixture
  10. concentrationconcentrate
  11. filtrationFilter the brown suspension
  12. concentrationconcentrate the mother liquors
  13. customto give a brown solution
  14. extractionExtract this solution with DCM (5×800 mL)
  15. concentrationconcentrate the organic layers
  16. filtrationFilter the aqueous layer through CELITE®
  17. customseparate the filtrates
  18. concentrationConcentrate all the combined organics

Sources & evidence

ORD record
ord-078f8d593ca94d2dad79d76ae981d9ba
Source dataset
uspto-grants-2015_07
Patent number
US09073856B2

Reaction notes

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