Trifluoroacetic acid → HCID 59371263, compound

HRID 2095397Notes

Reaction equation

HRID 2095397 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C@@H:12]1[CH2:16][CH2:15][N:14]([C:17]2[CH:18]=[N:19][CH:20]=[C:21]([O:23][CH2:24][C@@H:25]3[CH2:29][CH2:28][CH2:27][N:26]3C(OC(C)(C)C)=O)[CH:22]=2)[CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.O>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C@@H:12]1[CH2:16][CH2:15][N:14]([C:17]2[CH:18]=[N:19][CH:20]=[C:21]([O:23][CH2:24][C@@H:25]3[CH2:29][CH2:28][CH2:27][NH:26]3)[CH:22]=2)[CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59371579HCID 59371579, compound

Product 1

HCID 59371263HCID 59371263, compoundYield 70.1%

Reagents, catalysts & solvents 1

HCID 21908982Water methylene chlorideSolvent

Procedure

To a 25 mL round-bottom flask containing a solution of 3-[3(R)-[3-(benzyloxy)propyl]-1-pyrrolidinyl]-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (500 mg, 1.01 mmol) in CH2Cl2/H2O (7.5/0.15 mL) was added CF3COOH (1.5 mL) at 0° C. under N2. The reaction mixture was stirred for 3 h at room temperature. After evaporation under reduced pressure, the crude product (500 mg) was purified by preparative HPLC (column: SunFire Prep C18, 150×19 mm, 5 μm particle size; UV detection at 220 and 254 nm; flow 20 mL/min; mobile phase: A, water with 0.05% CF3COOH; B, methanol; 40-100% of B in A in 8 min, back to 40% in 1 min). The eluate was partially evaporated under reduced pressure (bath 30° C.) to remove CH3OH. The residue was basified with saturated aqueous NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with brine and dried over Na2SO4. After concentration in vacuo, the free base (280 mg, 70%) was obtained as a light-yellow solid. 1H NMR (CDCl3, 300 MHz) δ 7.65 (s, 1H), 7.61 (s, 1H), 7.37-7.33 (m, 5H), 6.33 (s, 1H), 4.54 (s, 2H), 4.01-3.97 (m, 2H), 3.69-3.59 (m, 1H), 3.53 (t, J=6.3 Hz, 2H), 3.50-3.20 (m, 4H), 3.09-3.06 (m, 2H), 2.90 (t, 1H, J=6.3 Hz), 2.38-2.10 (m, 2H), 2.03-1.83 (m, 3H), 1.79-1.51 (m, 5H). LC-MS (ESI) m/z 396 (M+H+).

Workup

  1. customAfter evaporation under reduced pressure
  2. customthe crude product (500 mg) was purified by preparative HPLC (column
  3. wait40-100% of B in A in 8 min
  4. waitback to 40% in 1 min)
  5. customThe eluate was partially evaporated under reduced pressure (bath 30° C.)
  6. customto remove CH3OH
  7. extractionextracted with EtOAc
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over Na2SO4
  10. concentrationAfter concentration in vacuo

Sources & evidence

ORD record
ord-6380789fa45942ed9c5ec5347e4a23d8
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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