Trifluoroacetic acid → HCID 86686244, compound

HRID 1021301Notes

Reaction equation

HRID 1021301 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[C:11]([F:33])=[C:12]([N:16]2[CH2:19][CH:18]([CH:20]3[CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH2:21]3)[CH2:17]2)[CH:13]=[CH:14][CH:15]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Si:1]([O:8][CH2:9][C:10]1[C:11]([F:33])=[C:12]([N:16]2[CH2:19][CH:18]([CH:20]3[CH2:21][CH2:22][NH:23][CH2:24][CH2:25]3)[CH2:17]2)[CH:13]=[CH:14][CH:15]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86686245HCID 86686245, compound

Product 1

HCID 86686244HCID 86686244, compoundYield 42.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 4-{1-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]azetidin-3-yl}piperidine-1-carboxylate (2 g) was mixed with CH2Cl2 (20 ml), and TFA (5 ml) was added thereto, followed by stirring at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. The obtained residue was mixed with CH2Cl2 (30 ml), and TEA (6 ml) and TBSCl (2.5 g) were added thereto, followed by stirring at 60° C. overnight. Water was added to the reaction mixture, and the organic layer was dried over Na2SO4 and then concentrated under reduced pressure. The obtained residue was mixed with MeOH (20 ml), and a 1 M aqueous NaOH solution (5 ml), followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, CHCl3 and water were added to the obtained residue, and the organic layer was dried over Na2SO4 and then concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (hexane/EtOAc) to obtain 4-{1-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]azetidin-3-yl}piperidine (673 mg).

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additionThe obtained residue was mixed with CH2Cl2 (30 ml), and TEA (6 ml) and TBSCl (2.5 g)
  4. additionwere added
  5. stirringby stirring at 60° C. overnight
  6. additionWater was added to the reaction mixture
  7. dry with materialthe organic layer was dried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. additionThe obtained residue was mixed with MeOH (20 ml)
  10. stirringby stirring at room temperature for 1 hour
  11. concentrationThe reaction mixture was concentrated under reduced pressure, CHCl3 and water
  12. additionwere added to the obtained residue
  13. dry with materialthe organic layer was dried over Na2SO4
  14. concentrationconcentrated under reduced pressure
  15. customThe obtained residue was purified by basic silica gel column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-7799d9b376b04742b0e6f36cc6c6a213
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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