Water → HCID 59371343, compound

HRID 2095437Notes

Reaction equation

HRID 2095437 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][O:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19]([N:21]2[CH2:25][CH2:24][C@@H:23]([CH2:26][O:27][CH2:28][CH2:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:22]2)[CH:20]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.O>C(Cl)Cl>[C:31]1([CH2:30][CH2:29][CH2:28][O:27][CH2:26][C@@H:23]2[CH2:24][CH2:25][N:21]([C:19]3[CH:18]=[N:17][CH:16]=[C:15]([O:14][CH2:13][C@@H:9]4[CH2:10][CH2:11][CH2:12][NH:8]4)[CH:20]=3)[CH2:22]2)[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 59371561HCID 59371561, compound

Product 1

HCID 59371343HCID 59371343, compoundYield 67.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]-5-[3(R)-[(3-phenylpropoxy)methyl]-1-pyrrolidinyl]pyridine (280 mg, 0.56 mmol) in CH2Cl2 (5 mL) was added a mixture of CF3COOH (1 mL) and water (0.1 mL) under N2. The solution was stirred overnight at room temperature. After concentration under vacuum, the crude product 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% TFA; B, MeOH; 0-6 min, 40% to 50% B in A; 6-7 min, 50%; 7-8 min, 100%). 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 concentration in vacuo, the free base (150 mg, 67%) was obtained as a yellowish oil. 1H NMR (CDCl3, 300 MHz) δ 7.67 (d, 1H, J=2.1 Hz), 7.64 (d, 1H, J=2.1 Hz), 7.32-7.19 (m, 5H), 6.37 (t, 1H, J=2.1 Hz), 4.03-3.96 (m, 2H), 3.64-3.60 (m, 1H), 3.49-3.29 (m, 7H), 3.13-3.01 (m, 3H), 2.90 (br s, 1H), 2.74-2.63 (m, 3H), 2.19-2.13 (m, 1H), 2.04-1.88 (m, 6H), 1.69-1.57(m, 1H). LC-MS (ESI) m/z 396 (M+H+).

Workup

  1. concentrationAfter concentration under vacuum
  2. customthe crude product was purified by preparative HPLC (column
  3. custom0-6 min, 40% to 50% B
  4. custom6-7 min, 50%
  5. custom7-8 min, 100%
  6. customThe eluate was partially evaporated under reduced pressure (bath 30° C.)
  7. customto remove CH3OH
  8. extractionextracted with EtOAc
  9. washThe combined organic layers were washed with brine
  10. customdried
  11. concentrationAfter concentration in vacuo

Sources & evidence

ORD record
ord-49339f1785df4ee38d7eb27e5679512d
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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