Water → HCID 68611056, compound

HRID 2095416Notes

Reaction equation

HRID 2095416 reaction equation
FC(F)(F)C(O)=O.O.[CH2:9]([O:16][CH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:26]=[N:27][CH:28]=[C:29]([O:31][CH2:32][C@H:33]3[CH2:36][CH2:35][N:34]3C(OC(C)(C)C)=O)[CH:30]=2)[CH2:21][CH2:20]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C(Cl)Cl>[NH:34]1[CH2:35][CH2:36][C@@H:33]1[CH2:32][O:31][C:29]1[CH:28]=[N:27][CH:26]=[C:25]([N:22]2[CH2:21][CH2:20][CH:19]([CH2:18][CH2:17][O:16][CH2:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH2:24][CH2:23]2)[CH:30]=1

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 68610949HCID 68610949, compound

Product 1

HCID 68611056HCID 68611056, compoundYield 63.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (1.5 mL) and water (0.15 mL) were added to CH2Cl2 (7.5 mL). This mixture was added to 3-[4-[2-(benzyloxy)ethyl]-1-piperidinyl]-5-[[1-(tert-butoxycarbonyl)-2(R)-azetidinyl]methoxy]pyridine (260 mg, 0.54 mmol) in a 25 mL round-bottom flask with a magnetic stirrer under N2. After stirring overnight at room temperature, TLC analysis of the crude reaction mixture indicated that the starting material had disappeared. The mixture was concentrated, and the residue was purified by preparative HPLC (column: SunFire Prep C18, 150×19 mm, 5 μm particle size; UV detection at 270 nm; mobile phase: A, water with 0.05% CF3COOH; B, methanol; 40-50% B in A in 6 min, up to 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 basified 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 base (130 mg, 63%) was obtained as a yellow oil. 1H NMR (CDCl3, 300 MHz) δ 7.97 (s, 1H), 7.79 (s, 1H), 7.38-7.28 (m, 5H), 6.78 (s, 1H), 4.53 (s, 2H), 4.43-4.41 (m, 1H), 4.15-4.09 (m, 2H), 3.85-3.82 (m, 1H), 3.70-3.66 (m, 2H), 3.58-3.50 (m, 2H), 2.79-2.71 (dd, 2H, J=7.2 Hz, 2.1 Hz), 2.47-2.39 (m, 2H), 1.82-1.78 (d, 2H, J=1.2 Hz), 1.64-1.58 (m, 3H), 1.40-1.27 (m, 3H). LC-MS (ESI) m/z 382 (M+H+).

Workup

  1. customTLC analysis of the crude reaction mixture
  2. concentrationThe mixture was concentrated
  3. customthe residue was purified by preparative HPLC (column
  4. wait40-50% B in A in 6 min
  5. waitup to 100% in 1 min
  6. waitback to 40% in 1 min)
  7. customThe eluate was partially evaporated under reduced pressure (bath 30° C.)
  8. customto remove CH3OH
  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-74e4460fa6f14f4fbb217e1ca8868e38
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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