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

HRID 2095346Notes

Reaction equation

HRID 2095346 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 593715891-[3-[5-[[1-(tert-Butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]phenyl]-3-phenyl-2(S)-propanol

Product 1

HCID 593713341-[3-[5-[(2(S)-azetidinyl)methoxy]-3-pyridyl]phenyl]-3-phenyl-2(S)-propanolYield 52%

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 a sample of 1-[3-[5-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]phenyl]-3-phenyl-2(S)-propanol (320 mg, 0.67 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 (300 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; 40-100% B in A in 8 min). The product-containing eluate was partially evaporated 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, 52%) as a yellow oil. 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 (300 mg) was purified by preparative HPLC (column
  8. wait40-100% B in A in 8 min)
  9. customThe product-containing eluate was partially evaporated 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-f91483e803924a91b14b5459b24db70a
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

Loading…