Water → HCID 59371410, compound

HRID 2095356Notes

Reaction equation

HRID 2095356 reaction equation
FC(F)(F)C(O)=O.O.C(OC([N:16]1[CH2:19][CH2:18][C@@H:17]1[CH2:20][O:21][C:22]1[CH:23]=[N:24][CH:25]=[C:26]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([CH2:34][C@@H:35]([O:43][CH3:44])[CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:29]=2)[CH:27]=1)=O)(C)(C)C>C(Cl)Cl>[NH:16]1[CH2:19][CH2:18][C@H:17]1[CH2:20][O:21][C:22]1[CH:23]=[N:24][CH:25]=[C:26]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([CH2:34][C@H:35]([O:43][CH3:44])[CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:29]=2)[CH:27]=1

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 68612208HCID 68612208, compound

Product 1

HCID 59371410HCID 59371410, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (1.6 mL) and water (0.16 mL) were added to 8 mL of CH2Cl2. This mixture was added to 3-[[1-(tert-butoxycarbonyl)-2(R)-azetidinyl]methoxy]-5-[3-(2(S)-methoxy-3-phenylpropyl)phenyl]pyridine (470 mg, 0.96 mmol) at 0° C. under N2. The solution was stirred overnight at room temperature. After concentration in vacuo, the crude product (300 mg) was purified by preparative HPLC (column: SunFire Prep C18, 150×19, 5 μm; UV detection, at 254 nm; mobile phase: A, water with 0.05% CF3COOH; B, CH3CN; 18-40% B in A in 6 min, 40-100% in 1 min). The product-containing eluate was partially evaporated under reduced pressure (bath 30° C.) to remove CH3CN. The pH of the residue was adjusted to 8.0 with saturated aqueous NaHCO3 solution, and the product was extracted into EtOAc (3×60 mL). The combined organic phases were washed with brine and dried over Na2SO4. After filtration and concentration, the free amine (175 mg, 47%) was obtained as a colorless oil. LC-MS (ESI) m/z 389 (M+H+).

Workup

  1. concentrationAfter concentration in vacuo
  2. customthe crude product (300 mg) was purified by preparative HPLC (column
  3. wait18-40% B in A in 6 min
  4. wait40-100% in 1 min)
  5. customThe product-containing eluate was partially evaporated under reduced pressure (bath 30° C.)
  6. customto remove CH3CN
  7. extractionthe product was extracted into EtOAc (3×60 mL)
  8. washThe combined organic phases were washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationAfter filtration and concentration

Sources & evidence

ORD record
ord-1a21a1343d7e4c569eebcceeca705a95
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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