Trifluoroacetic acid → N-[1-(Thiophen-2-ylmethyl)-piperidin-3-ylmethyl]-N-phenyl-propionamide

HRID 1246884Notes

Reaction equation

HRID 1246884 reaction equation
FC(F)(F)C(O)=O.[C:8]([N:15]1[CH2:20][CH2:19][CH2:18][CH:17]([CH2:21][N:22]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:23](=[O:26])[CH2:24][CH3:25])[CH2:16]1)(OC(C)(C)C)=O.[S:33]1[CH:37]=[CH:36][CH:35]=[C:34]1C=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[S:33]1[CH:37]=[CH:36][CH:35]=[C:34]1[CH2:8][N:15]1[CH2:20][CH2:19][CH2:18][CH:17]([CH2:21][N:22]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:23](=[O:26])[CH2:24][CH3:25])[CH2:16]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 73642-ThiophenecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 12991578N-(1-Boc-piperidin-3-ylmethyl)-N-phenyl-propionamide

Product 1

HCID 12108345N-[1-(Thiophen-2-ylmethyl)-piperidin-3-ylmethyl]-N-phenyl-propionamideYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.5 mL) was added dropwise to a solution of N-(1-Boc-piperidin-3-ylmethyl)-N-phenyl-propionamide 5 (31 mg, 0.090 mmol) in 0.5 mL of dry CH2Cl2 at 0° C. (ice-water). The reaction mixture was stirred at room temperature for 30 minutes. TLC showed the reaction was complete. After removal of the solvents, the residue was dried under vacuum for 3 hrs. The crude compound was dissolved in DMF (0.5 mL) and 2-thiophene carboxaldehyde (12.5 μL, 1.5 eq.) was added. The mixture was stirred at room temperature for 30 min. NaB(OAc)3H (95%, 28.45 mg, 1.5 eq.) was introduced in one portion, and the mixture was shaken at room temperature overnight. The mixture was quenched with 5 mL of aqueous potassium carbonate (sat.), then extracted with ethyl acetate (3×10 mL). The extracts were combined and washed with aqueous NaHCO3 (sat., 2×5 mL), brine (10 mL), and dried over anhydrous sodium sulfate. After the solvent was removed, the remaining oily residue was purified by preparative thin layer chromatography (EtOAc/MeOH, 9:1) to afford N-[1-(Thiophen-2-ylmethyl)-piperidin-3-ylmethyl]-N-phenyl-propionamide 8 as a colorless oil (25.2 mg, 82%). LRMS 343.

Workup

  1. customAfter removal of the solvents
  2. customthe residue was dried under vacuum for 3 hrs
  3. dissolutionThe crude compound was dissolved in DMF (0.5 mL)
  4. stirringThe mixture was stirred at room temperature for 30 min
  5. stirringthe mixture was shaken at room temperature overnight
  6. customThe mixture was quenched with 5 mL of aqueous potassium carbonate (sat.)
  7. extractionextracted with ethyl acetate (3×10 mL)
  8. washwashed with aqueous NaHCO3 (sat., 2×5 mL), brine (10 mL)
  9. dry with materialdried over anhydrous sodium sulfate
  10. customAfter the solvent was removed
  11. customthe remaining oily residue was purified by preparative thin layer chromatography (EtOAc/MeOH, 9:1)

Sources & evidence

ORD record
ord-5e5c62b2cde947deb8b6cc1eb7321625
Source dataset
uspto-grants-2006_10
Patent number
US07129228B2

Reaction notes

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