Acetic Anhydride → HCID 59516072, compound

HRID 1799406Notes

Reaction equation

HRID 1799406 reaction equation
[C:1]([CH2:3][C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])#[N:2].[CH:11](OCC)(OCC)OCC.C(OC(=O)C)(=O)C.Cl.[NH:29]([C:31]1[CH:36]=[CH:35][C:34]([CH2:37][C:38]([O:40][CH3:41])=[O:39])=[CH:33][CH:32]=1)[NH2:30].CCN(C(C)C)C(C)C>CO>[NH2:2][C:1]1[N:29]([C:31]2[CH:32]=[CH:33][C:34]([CH2:37][C:38]([O:40][CH3:41])=[O:39])=[CH:35][CH:36]=2)[N:30]=[CH:11][C:3]=1[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5]

Participants

7

Reactant 5

HCID 7918Acetic AnhydrideHCID 31214Ethyl orthoformateHCID 70693tert-Butyl cyanoacetateHCID 81531DiisopropylethylamineHCID 19593944252752-46-82×

Product 1

HCID 59516072HCID 59516072, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
125 °C

Procedure

t-Butyl cyanoacetate (3.525 g, 25 mmol) was dissolved in triethyl orthoformate (6.2 mL, 37.5 mmol). Acetic anhydride (2.41 mL, 25 mmol) was added and the mixture heated to 125° C. for 3 h. Volatiles were then removed by evaporation under reduced pressure to leave an orange oil. The crude oil was dissolved in methanol and methyl 2-(4-hydrazinylphenyl)acetate hydrochloride (Intermediate #39) (1.62 g, 7.5 mmol) and DIPEA (1.3 mL, 7.5 mmol) were added. The mixture was heated to reflux for 2 h and then evaporated to dryness. The residue was dissolved in ethyl acetate (100 mL), washed with water (2×50 mL) and brine (50 mL), dried (MgSO4) and evaporated to leave a crude to product which was purified by flash chromatography on silica gel (elution gradient 0-50% EtOAc in isohexane) to give the title compound as a yellow solid. (974 mg, 39%)

Workup

  1. customVolatiles were then removed by evaporation under reduced pressure
  2. customto leave an orange oil
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 2 h
  5. customevaporated to dryness
  6. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  7. washwashed with water (2×50 mL) and brine (50 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customto leave a crude to product which
  11. customwas purified by flash chromatography on silica gel (elution gradient 0-50% EtOAc in isohexane)

Sources & evidence

ORD record
ord-2fc5dfde05be46ac8b24c739143f2a06
Source dataset
uspto-grants-2013_01
Patent number
US08344016B2

Reaction notes

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