Acetic Anhydride → HCID 59516076, compound

HRID 1160544Notes

Reaction equation

HRID 1160544 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.[CH3:29][O:30][C:31](=[O:41])[C:32]1[CH:37]=[CH:36][C:35]([CH2:38][NH:39][NH2:40])=[CH:34][CH:33]=1.CCN(C(C)C)C(C)C>C(O)C.C(OCC)(=O)C>[C:7]([O:6][C:4]([C:3]1[CH:11]=[N:40][N:39]([CH2:38][C:35]2[CH:36]=[CH:37][C:32]([C:31]([O:30][CH3:29])=[O:41])=[CH:33][CH:34]=2)[C:1]=1[NH2:2])=[O:5])([CH3:10])([CH3:9])[CH3:8]

Participants

8

Reactant 5

HCID 7918Acetic AnhydrideHCID 31214Ethyl orthoformateHCID 70693tert-Butyl cyanoacetateHCID 81531DiisopropylethylamineHCID 67019495HCID 67019495, compound

Product 1

HCID 59516076HCID 59516076, compoundYield 60.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
125 °C

Procedure

t-Butyl cyanoacetate (600 mg, 4.25 mmol) was dissolved in triethyl orthoformate (1.06 ml, 6.38 mmol), acetic anhydride (0.40 ml, 4.25 mmol) was added and the mixture heated to 125° C. for 2 hours. The solution was evaporated to leave a yellow oil. This oil was redissolved in ethanol (5 ml) and treated with 4-Hydrazinomethyl-benzoic acid methyl ester hydrochloride (Intermediate#52) (230 mg, 1.06 mmol) and DIPEA (184 μl, 1.06 mmol). The resulting mixture was heated to reflux for 2 h and then cooled to ambient temperature and evaporated to leave a brown oil. This oil was dissolved in ethyl acetate (50 mL), washed with water (2×20 mL) and brine (20 mL) then dried (MgSO4), filtered and evaporated. The residue was chromatographed (40 g silica EtOAc/Hexane 0-50%) to yield the title compound as a yellow solid (214 mg, 43%).

Workup

  1. customThe solution was evaporated
  2. customto leave a yellow oil
  3. temperatureThe resulting mixture was heated
  4. temperatureto reflux for 2 h
  5. temperaturecooled to ambient temperature
  6. customevaporated
  7. customto leave a brown oil
  8. washwashed with water (2×20 mL) and brine (20 mL)
  9. dry with materialthen dried (MgSO4)
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was chromatographed (40 g silica EtOAc/Hexane 0-50%)

Sources & evidence

ORD record
ord-e0bd45757b8345a7859f354a42a99df4
Source dataset
uspto-grants-2010_10
Patent number
US07816391B2

Reaction notes

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