Trifluoroacetic acid → HCID 178520640, compound

HRID 1047379Notes

Reaction equation

HRID 1047379 reaction equation
C(O[C:6](=O)[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][CH2:15][C:16](=[O:33])[N:17]2[CH2:22][CH2:21][N:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)[CH2:19][CH2:18]2)[CH2:10][CH2:9]1)(C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+].FC1[CH:50]=[CH:51][C:52]([N+:59]([O-:61])=[O:60])=[C:53]([C:55]([F:58])([F:57])[F:56])[CH:54]=1>CS(C)=O.ClCCl>[N+:59]([C:52]1[CH:51]=[CH:50][C:6]([NH:7][C@H:8]2[CH2:9][CH2:10][C@H:11]([CH2:14][CH2:15][C:16]([N:17]3[CH2:22][CH2:21][N:20]([C:23]4[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=4)[CH2:19][CH2:18]3)=[O:33])[CH2:12][CH2:13]2)=[CH:54][C:53]=1[C:55]([F:56])([F:57])[F:58])([O-:61])=[O:60]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 2230945-Fluoro-2-nitrobenzotrifluorideHCID 178453886HCID 178453886, compound

Product 1

HCID 178520640HCID 178520640, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent2×

Procedure

(Trans-4-{3-oxo-3-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-propyl}-cyclohexyl)-carbamic acid tert-butyl ester (23 mg, 0.06 mmol, prepared in accordance with Example 40) was combined with a 50% (vol/vol) solution of trifluoroacetic acid and dichloromethane (3 mL). The resulting mixture was stirred for 30 min at room temperature. The mixture was then concentrated under vacuum to form a crude residue. The crude residue was dissolved in dimethylsulfoxide (3 mL). Afterward, potassium carbonate was added (17 mg, 0.12 mmol). 5-Fluoro-2-nitrobenzotrifluoride (15 mg, 0.07 mmol) was then added. The resulting mixture was reacted at 120° C. for 18 hr. The mixture was then cooled to room temperature, diluted with dichloromethane (15 mL), washed with water (4×8 mL), washed with saturated aqueous ammonium chloride (8 mL), washed with water (8 mL), washed with saturated aqueous hydrogencarbonate (2×8 mL), and washed with water (2×8 mL). The organic phase was collected, dried over magnesium sulfate, and concentrated under vacuum to form a crude residue. The crude residue was purified by preparative HPLC. Following lyophilization of the fractions of interest, the desired product was isolated as a solid (17 mg, 48% yield). The structure was confirmed using Protocol I-A. Calculated mass=573; observed mass=553; HPLC retention time=4.98 min. It is believed that the discrepancy between the actual and observed masses stems from a loss of HF upon ionization.

Workup

  1. concentrationThe mixture was then concentrated under vacuum
  2. customto form a crude residue
  3. customThe resulting mixture was reacted at 120° C. for 18 hr
  4. temperatureThe mixture was then cooled to room temperature
  5. washwashed with water (4×8 mL)
  6. washwashed with saturated aqueous ammonium chloride (8 mL)
  7. washwashed with water (8 mL)
  8. washwashed with saturated aqueous hydrogencarbonate (2×8 mL)
  9. washwashed with water (2×8 mL)
  10. customThe organic phase was collected
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated under vacuum
  13. customto form a crude residue
  14. customThe crude residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-ca85bd22e9044f03bac43a61141370e3
Source dataset
uspto-grants-2013_10
Patent number
US08569495B2

Reaction notes

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