Tetrahydrofuran → N-[(1S)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl]-L-leucine

HRID 2223525Notes

Reaction equation

HRID 2223525 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C@H:8]([NH:13][C@@H:14]([CH2:17][CH:18]([CH3:20])[CH3:19])[CH2:15][OH:16])[C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.C1C[O:24]CC1>>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C@H:8]([NH:13][C@H:14]([C:15]([OH:24])=[O:16])[CH2:17][CH:18]([CH3:20])[CH3:19])[C:9]([F:11])([F:12])[F:10])=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 86590543(2S)-2-{[(1S)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl]amino}-4-methylpentan-1-ol

Product 1

HCID 86590542N-[(1S)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl]-L-leucine

Procedure

A stock solution of H5IO6/CrO3 was prepared by dissolving H5IO6 (68.4 g, 0.3 mol) and CrO3 (138 mg, 1.2 mol %) in CH3CN (684 mL) to give a 0.44 M solution. To a solution of H5IO6/CrO3 (16 mmol, 36 mL, 0.44 M in THF) at −5° C. (ice and salt bath) was added a solution of (2S)-2-{[(1S)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl]amino}-4-methylpentan-1-ol (1 g) in 3 mL THF dropwise. The internal temperature was monitored and reaction temperature was not allowed to rise above 0° C. The reaction was monitored by TLC until the reaction was complete (3-4 h). Na2HPO4 (80 mL) was added to the reaction mixture which was then extracted with EtOAc. The organic extract was washed with brine, NaHSO3 (120 mL) and brine again, dried over anhyd. MgSO4 and concentrated to an oil. The oil was redissolved in EtOAc and filtered through a short pad of silica gel, eluted with EtOAc and the filtrated was concentrated to give the title compound.

Workup

  1. customreaction temperature
  2. customto rise above 0° C
  3. custom(3-4 h)
  4. extractionwas then extracted with EtOAc
  5. extractionThe organic extract
  6. washwas washed with brine, NaHSO3 (120 mL) and brine again
  7. customdried over anhyd
  8. concentrationMgSO4 and concentrated to an oil
  9. dissolutionThe oil was redissolved in EtOAc
  10. filtrationfiltered through a short pad of silica gel
  11. washeluted with EtOAc
  12. concentrationthe filtrated was concentrated

Sources & evidence

ORD record
ord-3dcc35d42ac74018b0e96f67b385ad28
Source dataset
uspto-grants-2008_05
Patent number
US07375134B2

Reaction notes

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