Chloride → HCID 58123722, compound

HRID 536678Notes

Reaction equation

HRID 536678 reaction equation
[Cl-].[CH3:2][NH:3][C:4](=O)[CH3:5].N1C(C)=CC=CC=1C.C(OC([N:22]1[CH2:29][CH2:28][C@:27]2([CH3:32])[C@H:30]([CH3:31])[C@H:23]1[CH2:24][C:25]1[CH:36]=[CH:35][C:34]([C:37]([NH:39][NH2:40])=O)=[CH:33][C:26]=12)=O)(C)(C)C>ClCCl>[CH3:2][N:3]1[C:4]([CH3:5])=[N:40][N:39]=[C:37]1[C:34]1[CH:35]=[CH:36][C:25]2[CH2:24][C@@H:23]3[C@@H:30]([CH3:31])[C@:27]([CH3:32])([C:26]=2[CH:33]=1)[CH2:28][CH2:29][NH:22]3

Participants

6

Reactant 4

HCID 312ChlorideHCID 6582N-MethylacetamideHCID 79372,6-LutidineHCID 58124006HCID 58124006, compound

Product 1

HCID 58123722HCID 58123722, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Oxalylic chloride (0.12 mL) is added to a solution N-methylacetamide (102 mg) and 2,6-lutidine (0.33 mL) in dichloromethane (5 mL) chilled in an ice bath. After stirring the solution for 15 min, (2R,6R,11S)-8-hydrazinocarbonyl-6,11-dimethyl-1,2,5,6-tetrahydro-4H-2,6-methano-benzo[d]azocine-3-carboxylic acid tert-butyl ester (0.50 g) is added and the cooling bath is removed. The resulting solution is stirred at ambient temperature for 1 h and then neutralized with aqueous NaHCO3 solution. The resulting mixture is extracted with dichloromethane, the combined organic extracts are dried (MgSO4), and the solvent is evaporated. The residue is taken up in acetic acid (3 mL) and stirred at 120° C. for 2.5 h. After cooling to room temperature, the mixture is concentrated under reduced pressure and the residue is taken up in trifluoroacetic acid (1 mL) and dichloromethane (5 mL) to cleave off the tert-butoxycarbonyl group. The solution is stirred at room temperature overnight and then concentrated. The residue is dissolved in little methanol/acetonitrile, neutralized with aqueous ammonia, and purified by HPLC on reversed phase (MeCN/H2O/NH4OH) to give the title compound.

Workup

  1. temperaturechilled in an ice bath
  2. customthe cooling bath is removed
  3. stirringThe resulting solution is stirred at ambient temperature for 1 h
  4. extractionThe resulting mixture is extracted with dichloromethane
  5. dry with materialthe combined organic extracts are dried (MgSO4)
  6. customthe solvent is evaporated
  7. stirringstirred at 120° C. for 2.5 h
  8. concentrationthe mixture is concentrated under reduced pressure
  9. stirringThe solution is stirred at room temperature overnight
  10. concentrationconcentrated
  11. dissolutionThe residue is dissolved in little methanol/acetonitrile
  12. custompurified by HPLC on reversed phase (MeCN/H2O/NH4OH)

Sources & evidence

ORD record
ord-c648d0241d19480a9c6fcde0958a88ea
Source dataset
uspto-grants-2014_10
Patent number
US08859580B2

Reaction notes

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