Trifluoroacetic acid → 4-[2-[1-[5-[(2(S)-Pyrrolidinyl)methoxy]-3-pyridyl]-4-piperidinyl]ethoxy]phenol

HRID 2095442Notes

Reaction equation

HRID 2095442 reaction equation
FC(F)(F)C(O)=O.[OH:8][C:9]1[CH:43]=[CH:42][C:12]([O:13][CH2:14][CH2:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:23]=[N:24][CH:25]=[C:26]([O:28][CH2:29][C@@H:30]4[CH2:34][CH2:33][CH2:32][N:31]4C(OC(C)(C)C)=O)[CH:27]=3)[CH2:18][CH2:17]2)=[CH:11][CH:10]=1>C(Cl)Cl.O>[NH:31]1[CH2:32][CH2:33][CH2:34][C@H:30]1[CH2:29][O:28][C:26]1[CH:27]=[C:22]([N:19]2[CH2:18][CH2:17][CH:16]([CH2:15][CH2:14][O:13][C:12]3[CH:42]=[CH:43][C:9]([OH:8])=[CH:10][CH:11]=3)[CH2:21][CH2:20]2)[CH:23]=[N:24][CH:25]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 593715663-[4-[2-(4-Hydroxyphenoxy)ethyl]-1-piperidinyl]-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine

Product 1

HCID 593715234-[2-[1-[5-[(2(S)-Pyrrolidinyl)methoxy]-3-pyridyl]-4-piperidinyl]ethoxy]phenolYield 58%

Reagents, catalysts & solvents 1

HCID 21908982Water methylene chlorideSolvent

Procedure

Trifluoroacetic acid (1.5 mL) was added slowly to a solution of 3-[4-[2-(4-hydroxyphenoxy)ethyl]-1-piperidinyl]-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (260 mg) in CH2Cl2/H2O (7.5/0.15 mL) at room temperature under N2. The solution was stirred overnight at room temperature. After removing the solvent, the residue was purified by preparative HPLC (column: SunFire Prep C18, 100×19 mm, 5 μm particle size; UV detection at 254 nm; flow 18 mL/min; mobile phase: A, water with 0.05% CF3COOH; B, CH3CN; 5% to 30% B in A in 6 min). The eluate was partially evaporated under reduced pressure (bath 30° C.) to remove CH3CN. 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 (108 mg, 58%) was obtained as a yellowish solid. LC-MS (ESI) m/z 398 (M+H+).

Workup

  1. customAfter removing the solvent
  2. customthe residue was purified by preparative HPLC (column
  3. wait5% to 30% B in A in 6 min)
  4. customThe eluate was partially evaporated under reduced pressure (bath 30° C.)
  5. customto remove CH3CN
  6. extractionextracted with EtOAc
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationAfter concentration in vacuo

Sources & evidence

ORD record
ord-5a02b389be7c444fa8ccbcbc5a0beb9e
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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