Trifluoroacetic acid → HCID 58996649, compound

HRID 1592736Notes

Reaction equation

HRID 1592736 reaction equation
C([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH2:20][NH2:21])[CH2:10][CH2:9]1)(OC(C)(C)C)=O.CCN(C(C)C)C(C)C.[C:31](Cl)(=[O:34])[CH2:32][CH3:33].C(O)(C(F)(F)F)=O.[OH-].[Na+]>C(Cl)Cl.C(OCC)(=O)C>[C:31]([NH:21][CH2:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[N:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1)(=[O:34])[CH2:32][CH3:33]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 62324Propionyl chlorideHCID 81531DiisopropylethylamineHCID 4961274Tert-butyl 4-[2-(aminomethyl)phenyl]piperazine-1-carboxylate

Product 1

HCID 58996649HCID 58996649, compoundYield 44.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

1-Boc-4-(2-aminomethyl-phenyl)-piperazine (0.75 g, 2.6 mmol) was dissolved in methylene chloride (20 mL), treated with DIPEA (2.3 mL, 13 mmol), and cooled to about 0° C. Propionyl chloride (0.20 mL, 2.34 mmol) was added and the mixture was stirred for about 1 hour at 0° C. and subsequently stirred overnight at r.t. The mixture is diluted with ethyl acetate (400 mL), washed with water (45 mL), saturated aqueous sodium bicarbonate (45 mL) and brine (45 mL), and then dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by silica gel chromatography (50% ethyl acetate in hexanes) gave an oil, which was dissolved in methylene chloride (10 mL). The mixture was stirred with TFA (10 mL) for about 1.5 hours. The mixture was concentrated under reduced pressure, and the residue taken up in water (25 mL). Sodium hydroxide (1.0 g, 25 mmol) and ethyl acetate (25 mL) were added and the mixture was stirred for about 45 minutes. The organic phase was collected and the aqueous phase was extracted with ethyl acetate (45 mL). The combined organic fractions were washed with water (20 mL) and brine (20 mL) and then dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure to yield the title compound (0.26 g, 40%) as a clear oil.

Workup

  1. washwashed with water (45 mL), saturated aqueous sodium bicarbonate (45 mL) and brine (45 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationConcentration under reduced pressure
  4. customgave an oil, which
  5. concentrationThe mixture was concentrated under reduced pressure
  6. stirringthe mixture was stirred for about 45 minutes
  7. customThe organic phase was collected
  8. extractionthe aqueous phase was extracted with ethyl acetate (45 mL)
  9. washThe combined organic fractions were washed with water (20 mL) and brine (20 mL)
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationThe solvent was concentrated under reduced pressure

Sources & evidence

ORD record
ord-a23c4e35e9b74c5a8553033b3dc4b769
Source dataset
uspto-grants-2007_11
Patent number
US07291619B2

Reaction notes

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