Methyl chloroformate → HCID 21465533, compound

HRID 1939985Notes

Reaction equation

HRID 1939985 reaction equation
Cl.[NH2:2][CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:5][CH2:4]1.C(N(CC)CC)C.Br[CH:25]([CH3:34])[C:26]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:27].[CH3:35][O:36]C(Cl)=O>ClCCl>[CH3:34][C:25]1[N:2]([CH:3]2[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:5][CH2:4]2)[C:35](=[O:36])[O:27][C:26]=1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 6586Methyl chloroformateHCID 8471Triethylamine2×HCID 164522-BromopropiophenoneHCID 127418611-(2-Phenylethyl)piperidin-4-amine--hydrogen chloride (1/1)

Product 1

HCID 21465533HCID 21465533, compoundYield 5.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of a 4-amino-1-phenethyl-piperidine hydrochloride (Example 8c, 2 g, 0.0072 Mol) and triethylamine (3.31 ml, 3.3 Mol eq) in dichloromethane (30 ml) was added 2-bromopropiophenone (1.54 g, 1 Mol eq) and the reaction mixture was stirred for 14 h at room temperature. After ice-bath cooling, methylchloroformate (3.36 ml, 6 Mol eq) was added and the reaction mixture stirred for a further 1 h. Triethylamine (5 ml) was added and the reaction mixture was concentrated in vacuo. The residue was redissolved in methanol (50 ml) and sodium methoxide (3 g) was added. After stirring at room temperature for 0.5 h, the reaction mixture was heated under reflux for 1h. After cooling, the solution was concentrated under vacuum and the residue obtained was partitioned between dichloromethane and water then dried (MgSO4), filtered and evaporated. The crude product was purified on a silica gel column using 0 to 2% methanol in dichloromethane as eluent then recrystallised from diethyl ether/hexane to give the title compound as a colourless solid (0.14 g, 5%). Mp 144° C. 1H NMR (DMSO) δ 1.72 (2H, m), 2.08 (2H, m), 2.30 (3H s), 2.33 (2H, m), 2.50 (2H, m), 2.75 (2H, m), 3.04 (2H, s), 3.69 (1H, m), 7.16-7.33 (5H, m), 7.42-7.47 (5H, m); MS (CI) m/e 363 [MH]+. Anal. Found C, 76.10; H, 7.19; N, 7.61. C23H26 ClN3O. 0.35H2O requires C, 76.21; H, 7.23; N, 7.73%.

Workup

  1. temperatureAfter ice-bath cooling
  2. stirringthe reaction mixture stirred for a further 1 h
  3. concentrationthe reaction mixture was concentrated in vacuo
  4. dissolutionThe residue was redissolved in methanol (50 ml)
  5. additionsodium methoxide (3 g) was added
  6. stirringAfter stirring at room temperature for 0.5 h
  7. temperaturethe reaction mixture was heated
  8. temperatureunder reflux for 1h
  9. temperatureAfter cooling
  10. concentrationthe solution was concentrated under vacuum
  11. customthe residue obtained
  12. customwas partitioned between dichloromethane and water
  13. dry with materialthen dried (MgSO4)
  14. filtrationfiltered
  15. customevaporated
  16. customThe crude product was purified on a silica gel column
  17. customthen recrystallised from diethyl ether/hexane

Sources & evidence

ORD record
ord-a2b9aa786977418fa47501369e763c70
Source dataset
uspto-grants-1997_12
Patent number
US05698573

Reaction notes

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