Water → 1-[3-[5-[(2(S)-azetidinyl)methoxy]-3-pyridyl]phenyl]-3-phenyl-2(R)-propanol

HRID 2095350Notes

Reaction equation

HRID 2095350 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]=[C:24]([C:28]2[CH:29]=[C:30]([CH2:34][C@H:35]([OH:43])[CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:31]=[CH:32][CH:33]=2)[CH:25]=[N:26][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]=[C:24]([C:28]2[CH:29]=[C:30]([CH2:34][C@H:35]([OH:43])[CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:31]=[CH:32][CH:33]=2)[CH:25]=[N:26][CH:27]=1

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 59371623HCID 59371623, compound

Product 1

HCID 461913501-[3-[5-[(2(S)-azetidinyl)methoxy]-3-pyridyl]phenyl]-3-phenyl-2(R)-propanolYield 43.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (1.6 mL) and water (0.16 mL) were added to CH2Cl2 (8.0 mL). This mixture was added to 1-[3-[5-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]phenyl]-3-phenyl-2(R)-propanol (381 mg, 0.80 mmol) in a 25 mL round-bottom flask with magnetic stirrer under N2. After stirring at room temperature overnight, the solution was concentrated in vacuo, the residue was diluted with water, and the solution was basified with saturated aqueous NaHCO3 solution and extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine and dried over Na2SO4. After filtration and concentration, the crude product (250 mg) was purified by preparative HPLC (column: SunFire Prep C18, 150×19, 5 μm particle size; UV detection at 254 nm; flow 20 mL/min; mobile phase: A, water with 0.05% TFA; B, methanol; 40-70% B in A in 6 min). The product-containing eluate was partially concentrated under reduced pressure to remove MeOH. The residual solution was basified with saturated aqueous NaHCO3 solution and extracted with EtOAc (3×50 mL). The combined organic phases were washed with brine and dried over Na2SO4. Concentration gave the free amine (130 mg, 43%) as a white solid. LC-MS (ESI) m/z 375 (M+H+).

Workup

  1. concentrationthe solution was concentrated in vacuo
  2. additionthe residue was diluted with water
  3. extractionextracted with EtOAc (3×50 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationAfter filtration and concentration
  7. customthe crude product (250 mg) was purified by preparative HPLC (column
  8. wait40-70% B in A in 6 min)
  9. concentrationThe product-containing eluate was partially concentrated under reduced pressure
  10. customto remove MeOH
  11. extractionextracted with EtOAc (3×50 mL)
  12. washThe combined organic phases were washed with brine
  13. dry with materialdried over Na2SO4
  14. concentrationConcentration

Sources & evidence

ORD record
ord-f5f91b9cb206430b9faf9e2213569e05
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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