Acetic Anhydride → Tert-butyl 5-amino-1-(4-methoxycarbonylphenyl)pyrazole-4-carboxylate

HRID 1799388Notes

Reaction equation

HRID 1799388 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:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=1)[NH2:30].CCN(C(C)C)C(C)C>C(OCC)(=O)C>[NH2:2][C:1]1[N:29]([C:31]2[CH:32]=[CH:33][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:39][CH:40]=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 2788448Methyl 4-hydrazinobenzoate hydrochloride2×

Product 1

HCID 57437895Tert-butyl 5-amino-1-(4-methoxycarbonylphenyl)pyrazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
125 °C

Procedure

t-Butyl cyanoacetate (14.1 g, 100 mmol) was dissolved in triethyl orthoformate (24.8 mL, 150 mmol). Acetic anhydride (9.625 mL, 100 mL) was added and the mixture heated to 125° C. for 3 h and then volatiles were removed by evaporation under reduced pressure. The residue was dissolved in ethanol (100 mL) and methyl 4-hydrazinylbenzoate hydrochloride (Intermediate #123) (6.06 g, 30 mmol) and DIPEA (5.23 mL, 30 mmol) was added. The mixture was heated to reflux for 5 h and then evaporated under reduced pressure to leave a brown oil which was dissolved in ethyl acetate (300 mL) and washed with water (2×100 mL) and brine (100 mL), dried (MgSO4) and evaporated. The residue was purified by chromatography on silica gel (120 g silica, EtOAc/Hexane 0-50%) to give the title compound as a yellow solid. (7.1 g)

Workup

  1. customvolatiles were removed by evaporation under reduced pressure
  2. dissolutionThe residue was dissolved in ethanol (100 mL)
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 5 h
  5. customevaporated under reduced pressure
  6. customto leave a brown oil which
  7. washwashed with water (2×100 mL) and brine (100 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customThe residue was purified by chromatography on silica gel (120 g silica, EtOAc/Hexane 0-50%)

Sources & evidence

ORD record
ord-308757ba60f942fab6cbed85526ee49a
Source dataset
uspto-grants-2013_01
Patent number
US08344016B2

Reaction notes

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