Pyrrolidine → HCID 69411027, compound

HRID 1592748Notes

Reaction equation

HRID 1592748 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[C:15]=2[CH:24]=O)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1.[BH4-].[Na+]>CO>[C:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[C:15]=2[CH2:24][N:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 4311764Sodium borohydrideHCID 17952247HCID 17952247, compound

Product 1

HCID 69411027HCID 69411027, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-boc-4-(2-formyl-3-trifluoromethyl-phenyl)piperazine (358 mg, 1 mmol, 1.0 eq.) in MeOH (10 mL) was added pyrrolidine (0.093 mL, 1.1 mmol, 1.1 eq.). The mixture was refluxed overnight. The reaction was cooled to about 0° C., and NaBH4 on alumina (10 wt % on basic alumina, 570 mg, 1.5 mmol, 1.5 eq.) was added. After the addition was compete, the ice bath was removed, and the mixture was stirred at r.t. for about 2 hours. The mixture was filtered through celite, washed with methanol and concentrated. The solution was diluted with EtOAc (50 mL) and washed with saturated NaHCO3 and brine. The aqueous layers were extracted with EtOAc (2×). The combined organic extracts were dried (Na2SO4), filtered and concentrated. Purification by flash chromatography (35 g SiO2, 40 mL/min, linear gradient 0-10% MeOH/CH2Cl2 for 25 minutes and 10% MeOH/CH2Cl2 for 7 minutes) gave the title compound (298 mg, 0.72 mmol, 72%). LRMS (ESI+): 414.3 (M+1)

Workup

  1. temperatureThe mixture was refluxed overnight
  2. additionAfter the addition
  3. customthe ice bath was removed
  4. filtrationThe mixture was filtered through celite
  5. washwashed with methanol
  6. concentrationconcentrated
  7. additionThe solution was diluted with EtOAc (50 mL)
  8. washwashed with saturated NaHCO3 and brine
  9. extractionThe aqueous layers were extracted with EtOAc (2×)
  10. dry with materialThe combined organic extracts were dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by flash chromatography (35 g SiO2, 40 mL/min, linear gradient 0-10% MeOH/CH2Cl2 for 25 minutes and 10% MeOH/CH2Cl2 for 7 minutes)

Sources & evidence

ORD record
ord-11be92c26f0b4997a723accf799d6553
Source dataset
uspto-grants-2007_11
Patent number
US07291619B2

Reaction notes

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