Trifluoroacetic acid → HCID 59452651, compound

HRID 419442Notes

Reaction equation

HRID 419442 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]3)[CH2:12][CH2:11]2)=[CH:6][C:5]=1[O:29][CH2:30][C:31]([F:34])([F:33])[F:32])([O-:3])=[O:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:11][CH2:12][CH:13]([N:16]3[CH2:17][CH2:18][NH:19][CH2:20][CH2:21]3)[CH2:14][CH2:15]2)=[CH:6][C:5]=1[O:29][CH2:30][C:31]([F:34])([F:33])[F:32])([O-:3])=[O:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59452658HCID 59452658, compound

Product 1

HCID 59452651HCID 59452651, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1,1-Dimethylethyl 4-(1-{4-nitro-3-[(2,2,2-trifluoroethyl)oxy]phenyl}-4-piperidinyl)-1-piperazinecarboxylate (1.35 g, 2.76 mmol) was dissolved in 40 mL of DCM with stirring. TFA (10.0 mL, 130 mmol) was added via syringe, and the reaction was stirred for 3 h and cooled to 0° C. The reaction was quenched with 20 mL of 6N NaOH (aqueous). Saturated NaHCO3 (aqueous) was added until the pH was approximately 9. The mixture was poured into H2O and DCM. The layers were separated, and the aqueous layer was washed with 4:1 DCM/iPrOH (2×) and 4:1 EtOAc/iPrOH. The combined organic layers was dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash chromatography afforded 0.879 g (82%) of the title compound of step E. 1H NMR (400 MHz, DMSO-d6) δ 7.85 (d, J=9.5 Hz, 1H), 6.63 (dd, J=9.5, 2.4 Hz, 1H), 6.55 (d, J=2.4 Hz, 1H), 4.88 (q, J=8.7 Hz, 2H), 4.02 (d, J=13.6 Hz, 2H), 2.84-2.98 (m, 2H), 2.56-2.67 (m, 4H), 2.26-2.49 (m, 5H), 1.96 (br. s., 1H), 1.70-1.84 (m, 2H), 1.38 (d, J=8.2 Hz, 2H).

Workup

  1. stirringthe reaction was stirred for 3 h
  2. customThe reaction was quenched with 20 mL of 6N NaOH (aqueous)
  3. additionSaturated NaHCO3 (aqueous) was added until the pH was approximately 9
  4. additionThe mixture was poured into H2O and DCM
  5. customThe layers were separated
  6. washthe aqueous layer was washed with 4:1 DCM/iPrOH (2×) and 4:1 EtOAc/iPrOH
  7. dry with materialThe combined organic layers was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by flash chromatography

Sources & evidence

ORD record
ord-3241fc35db624725805b6eb7266a747b
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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