Trifluoroacetic acid → 3-{4-[6-(4-Cyclohexyl-3-trifluoromethyl-phenoxymethyl)-pyridin-3-yl]-piperazin-1-yl}-propionic acid

HRID 2100668Notes

Reaction equation

HRID 2100668 reaction equation
[CH:1]1([C:7]2[CH:33]=[CH:32][C:10]([O:11][CH2:12][C:13]3[N:18]=[CH:17][C:16]([N:19]4[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]4)=[CH:15][CH:14]=3)=[CH:9][C:8]=2[C:34]([F:37])([F:36])[F:35])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O.[C:45]([O:49]C(C)(C)C)(=[O:48])[CH:46]=[CH2:47].CCN(C(C)C)C(C)C>C(Cl)Cl.CO>[CH:1]1([C:7]2[CH:33]=[CH:32][C:10]([O:11][CH2:12][C:13]3[N:18]=[CH:17][C:16]([N:19]4[CH2:24][CH2:23][N:22]([CH2:47][CH2:46][C:45]([OH:49])=[O:48])[CH2:21][CH2:20]4)=[CH:15][CH:14]=3)=[CH:9][C:8]=2[C:34]([F:36])([F:35])[F:37])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 15458tert-Butyl acrylateHCID 81531DiisopropylethylamineHCID 68815760Tert-butyl 4-[6-(4-cyclohexyl-3-trifluoromethyl-phenoxymethyl)-pyridin-3-yl]-piperazine-1-carboxylate

Product 1

HCID 116201463-{4-[6-(4-Cyclohexyl-3-trifluoromethyl-phenoxymethyl)-pyridin-3-yl]-piperazin-1-yl}-propionic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-[6-(4-cyclohexyl-3-trifluoromethyl-phenoxymethyl)-pyridin-3-yl]-piperazine-1-carboxylate (0.021 mmol) in DCM (1 mL) is added trifluoroacetic acid (2 mL). The reaction mixture is stirred at room temperature for 1 hour and evaporated to dryness. The residue is mixed with tert-butyl acrylate (0.3 mmol) and DIEA (0.6 mmol) in MeOH (1.5 mL). The mixture is heated in a microwave oven at 90° C. for 30 minutes and evaporated to dryness. To a solution of the residue in DCM (1.5 mL) is added trifluoroacetic acid (1.5 mL). The reaction mixture is stirred at room temperature for 1 hour. After concentration, the crude residue is purified by preparative RP LC-MS to give 3-{4-[6-(4-Cyclohexyl-3-trifluoromethyl-phenoxymethyl)-pyridin-3-yl]-piperazin-1-yl}-propionic acid. 1H NMR (400 MHz, CD3OD) δ 1.18-1.79 (10H), 2.75 (t, J=11.2 Hz, 1H), 2.80 (t, J=6.8 Hz, 2H), 3.37-3.78 (8H), 3.43 (t, J=6.8 Hz, 2H), 5.16 (s, 2H), 7.13 (dd, J=8.4, 2.8 Hz, 1H), 7.15 (s, 1H), 7.39 (d, J=8.4 Hz, 1H), 7.66 (d, J=8.8 Hz, 1H), 7.75 (dd, J=8.8, 2.8 Hz, 1H), 8.30 (s, 1H); ESI-MS m/z 492.2 (MH+).

Workup

  1. customevaporated to dryness
  2. temperatureThe mixture is heated in a microwave oven at 90° C. for 30 minutes
  3. customevaporated to dryness
  4. additionTo a solution of the residue in DCM (1.5 mL) is added trifluoroacetic acid (1.5 mL)
  5. stirringThe reaction mixture is stirred at room temperature for 1 hour
  6. concentrationAfter concentration
  7. customthe crude residue is purified by preparative RP LC-MS

Sources & evidence

ORD record
ord-7a4ff7e8cd9e4111905ce5fa89c496a7
Source dataset
uspto-grants-2009_08
Patent number
US07572811B2

Reaction notes

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