Ethyl chloroformate → HCID 11537578, compound

HRID 1282098Notes

Reaction equation

HRID 1282098 reaction equation
[C:1]1([N:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]4(C(O)=O)[CH2:22][CH2:21]4)=[CH:16][CH:15]=3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)[O:27][CH2:28][CH3:29].[N-:32]=[N+]=[N-].[Na+].C[Mg]Br>O1CCCC1.O.C1C=CC=CC=1.CO.C(OCC)(=O)C.C(N(CC)CC)C>[C:1]1([N:7]2[CH2:8][CH2:9][N:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]4([NH:32][C:28](=[O:27])[CH3:29])[CH2:22][CH2:21]4)=[CH:16][CH:15]=3)[CH2:11][CH2:12]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

11

Reactant 4

HCID 10928Ethyl chloroformateHCID 33557Sodium AzideHCID 18423086HCID 18423086, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 11537578HCID 11537578, compound

Reagents, catalysts & solvents 6

HCID 241BenzeneSolventHCID 887MethanolSolventHCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (4-((4-phenylpiperazin-1-yl)methyl)-phenylcyclopropanecarboxylic acid (1.0 g) and triethylamine (0.42 ml) in tetrahydrofuran (70 ml) was added ethyl chlorocarbonate (0.29 ml) under ice-cooling and the mixture was stirred at 0° C. for 1 hr and 20 min. To this solution was added a solution of sodium azide (0.2 g) in water (3 ml) under ice-cooling, and the mixture was stirred for 30 min and left standing overnight. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated to give a brown oil. The oil was dissolved in benzene (20 ml) and refluxed under heating for 40 min. The reaction mixture was ice-cooled and methylmagnesium bromide (3M, tetrahydrofuran solution) (0.93 ml) was added dropwise. The mixture was stirred at room temperature for 1 hr. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated to give a colorless oil. The oil was subjected to silica gel column chromatography (developing solvent; ethyl acetate:methanol=20:1) to give a white solid. This solid was recrystallized from ethyl acetate-isopropyl ether to give the title compound (0.52 g) as white crystals, m.p.=129-139.5° C.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture was stirred for 30 min
  4. waitleft
  5. waitstanding overnight
  6. extractionextracted with ethyl acetate
  7. washThe extract was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customThe solvent was evaporated
  10. customto give a brown oil
  11. temperaturerefluxed
  12. temperatureunder heating for 40 min
  13. temperaturecooled
  14. stirringThe mixture was stirred at room temperature for 1 hr
  15. extractionextracted with ethyl acetate
  16. washThe extract was washed with saturated brine
  17. dry with materialdried over anhydrous magnesium sulfate
  18. customThe solvent was evaporated
  19. customto give a colorless oil
  20. customto give a white solid
  21. customThis solid was recrystallized from ethyl acetate-isopropyl ether

Sources & evidence

ORD record
ord-beb3e0b19ec34f9ebca943d5e4586a5b
Source dataset
uspto-grants-2002_09
Patent number
US06455528B1

Reaction notes

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