Trifluoroacetic acid → HCID 59371584, compound

HRID 2095403Notes

Reaction equation

HRID 2095403 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 59371457HCID 59371457, compound

Product 1

HCID 59371584HCID 59371584, 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(S)-[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 (310 mg) was purified by preparative HPLC (column: SunFire Prep C18, 150×19 mm, 5 μm particle size; UV detection at 270 nm; flow 20 mL/min; mobile phase: A, water with 0.05% CF3COOH; B, methanol; 40-50% B in A in 6 min, 50-100% in 1 min, back to 40% in 1 min). The eluate was partially evaporated under reduced pressure (bath 30° C.) to remove CH3OH. The residue was washed with saturated aqueous NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with brine and dried. After concentrated in vacuo, the free amine (280 mg, 70%) was obtained as light-yellow solid. 1H NMR (CDCl3, 300 MHz) δ 7.66 (s, 1H), 7.61 (s, 1H), 7.37-7.30 (m, 5H), 6.34 (s, 1H), 4.54 (s, 2H), 4.01-3.94 (m, 2H), 3.54-3.49 (m, 3H), 3.48-3.22 (m, 3H), 3.12-3.00 (m, 2H), 2.91 (t, 1H , J=9.6 Hz), 2.36-2.23 (m, 1H), 2.21-2.10 (m, 1H), 2.06-1.79 (m, 3H), 1.76-1.50 (m, 6H). LC-MS (ESI) m/z 396 (M+H+).

Workup

  1. customAfter evaporation under reduced pressure
  2. customthe crude product (310 mg) was purified by preparative HPLC (column
  3. wait40-50% B in A in 6 min
  4. wait50-100% in 1 min
  5. waitback to 40% in 1 min)
  6. customThe eluate was partially evaporated under reduced pressure (bath 30° C.)
  7. customto remove CH3OH
  8. washThe residue was washed with saturated aqueous NaHCO3 solution
  9. extractionextracted with EtOAc
  10. washThe combined organic layers were washed with brine
  11. customdried
  12. concentrationAfter concentrated in vacuo

Sources & evidence

ORD record
ord-d3ef396cb17c45d89501045e35405c1b
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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