Benzoic anhydride → HCID 178499093, compound

HRID 1013000Notes

Reaction equation

HRID 1013000 reaction equation
[NH2:1]/[C:2](=[N:21]/O)/[CH:3]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:4][O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.CO[C:25]([C:27]#[C:28][C:29]([O:31][CH3:32])=[O:30])=[O:26].[C:33]([O:41]C(=O)C1C=CC=CC=1)(=[O:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>C(Cl)(Cl)Cl>[C:33]([O:41][C:27]1[C:28]([C:29]([O:31][CH3:32])=[O:30])=[N:1][C:2]([CH:3]([NH:13][C:14]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:20])[CH2:4][O:5][CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:21][C:25]=1[OH:26])(=[O:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

5

Reactant 3

HCID 7167Benzoic anhydrideHCID 12980Dimethyl acetylenedicarboxylateHCID 149433868HCID 149433868, compound

Product 1

HCID 178499093HCID 178499093, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

tert-Butyl [(2E)-2-amino-1-[(benzyloxy)methyl]-2-(hydroxyimino)ethyl]carbamate prepared as described in Step 1 was dissolved in chloroform and treated with 1.2 eq. of dimethylacetylenedicarboxylate and the reaction was refluxed for 2.5 hours. After cooling at room temperature, the reaction mixture was concentrated and the solvent switched to xylene. The mixture was heated at 145° C. for 24 hours. After cooling at room temperature, solid material was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in dry CH2Cl2 then dry pyridine was added and finally benzoic anhydride (1.1 eq.). The mixture was stirred at room temperature overnight, then the solvent was removed by rotary evaporation and the residue taken in ethyl acetate was washed with 1 N HCl, sat. NaHCO3 and brine. Organic layer was separated, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (SiO2, eluting with 60/40 v/v petroleum ether/ethyl acetate), collection and evaporation of appropriate fractions afforded title product.

Workup

  1. temperaturethe reaction was refluxed for 2.5 hours
  2. concentrationthe reaction mixture was concentrated
  3. temperatureThe mixture was heated at 145° C. for 24 hours
  4. temperatureAfter cooling at room temperature
  5. filtrationsolid material was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. dissolutionThe residue was dissolved in dry CH2Cl2
  8. additiondry pyridine was added
  9. customthe solvent was removed by rotary evaporation
  10. washwas washed with 1 N HCl, sat. NaHCO3 and brine
  11. customOrganic layer was separated
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe resulting residue was purified by flash chromatography (SiO2, eluting with 60/40 v/v petroleum ether/ethyl acetate), collection and evaporation of appropriate fractions

Sources & evidence

ORD record
ord-270d0a4947464efba9f14e94e83364b5
Source dataset
uspto-grants-2011_07
Patent number
US07981879B2

Reaction notes

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