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

HRID 988763노트

반응식

HRID 988763 반응식
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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-c30f59819a724cd89d74d0a57c0c00ce
출처 데이터셋
uspto-grants-2003_10
특허 번호
US06635661B2

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