Triethylamine → HCID 18918657, compound

HRID 1290844Notes

Reaction equation

HRID 1290844 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:14][CH2:15][CH2:16][C:17](Cl)=[O:18].C(N(CC)CC)C>C(Cl)Cl>[Cl:14][CH2:15][CH2:16][C:17]([N:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]1)=[O:18]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 693643-Chloropropionyl chlorideHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 18918657HCID 18918657, compoundYield 41.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

4-(t-butoxycarbonyl)piperazine (3 g, 16 mmol) was suspended in 10 mL of methylene chloride and cooled in an ice/water bath. 3-Chloropropionyl chloride (2.04 g, 16 mmol) was dissolved in 10 mL of methylene chloride and added slowly, while maintaining the internal temperature below 50° C. Triethylamine (1.63 g, 16 mmol) was then added to the cold (50° C.) solution. The solution was slowly warmed to room temperature and then stirred at room temperature overnight. The reaction mixture was diluted with 150 mL of methylene chloride and washed with 5% aqueous NaHCO3 (2×100 mL), brine (2×100 mL), dried over MgSO4, filtered, concentrated and dried under vacuum to give 3.71 g of crude product. The crude material was purified by flash chromatography on silica gel eluting with ethyl acetate to give 1.85 g (41.8%) of 1-(3-chloropropionyl)-4-(t-butoxycarbonyl)piperazine as a pale yellow solid. 1H NMR (300 MHz/CDCl3): δ 1.47 (s, 9H), 2.82 (t, 2H, J=6.95 Hz), 3.40-3.46 (m, 6H), 3.60-3.63 (m, 2H), 3.84 (t, 2 H, J=6.95 Hz); mass spectrum, m/z=283.1 (M+Li); high-resolution FAB-MS calcd for C12H21N2O3Cl1 276.1240 (M+), found 276.1227.

Workup

  1. temperaturecooled in an ice/water bath
  2. additionadded slowly
  3. temperaturewhile maintaining the internal temperature below 50° C
  4. washwashed with 5% aqueous NaHCO3 (2×100 mL), brine (2×100 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customdried under vacuum
  9. customto give 3.71 g of crude product
  10. customThe crude material was purified by flash chromatography on silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-22b8e15546f64b6e8950bf7a161a1dfa
Source dataset
uspto-grants-1998_05
Patent number
US05753660

Reaction notes

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