Methyl acetoacetate → 1-tert-butyl-5-methyl-1H-pyrazole-4-carboxylic acid

HRID 570194Notes

Reaction equation

HRID 570194 reaction equation
C([O-])(=O)C.[Na+].[C:6]([O:12]C)(=[O:11])[CH2:7][C:8]([CH3:10])=O.C[N:15]([CH:17]([O:20]C)[O:18][CH3:19])C.Cl.[C:23]([NH:27][NH2:28])([CH3:26])([CH3:25])[CH3:24]>C(N(CC)CC)C>[C:23]([N:27]1[C:8]([CH3:10])=[C:7]([C:6]([OH:12])=[O:11])[CH:17]=[N:15]1)([CH3:26])([CH3:25])[CH3:24].[C:23]([N:27]1[C:8]([CH3:10])=[C:7]([C:17]([O:18][CH3:19])=[O:20])[CH:6]=[N:28]1)([CH3:26])([CH3:25])[CH3:24]

Participants

7

Reactant 4

HCID 7757Methyl acetoacetateHCID 78373Dimethylformamide dimethyl acetalHCID 81889tert-Butylhydrazine monohydrochlorideHCID 517045Sodium Acetate

Product 2

HCID 222279031-tert-butyl-5-methyl-1H-pyrazole-4-carboxylic acidHCID 50853230Methyl 1-tert-butyl-5-methyl-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

The title compound was prepared according to the procedure as described in Anderson, K. W., et al., PCT Publication, WO 2007/107470, published Sep. 27, 2007, as described in Example 54, Steps 2 and 3, pages 97-98, and substituting triethylamine for the sodium acetate reagent in Step 2) from methyl acetoacetate (1.14 mL, 10.6 mmol), DMFDMA (1.48 mL, 11.1 mmol), tert-butylhydrazine hydrochloride (1.32 g, 10.6 mmol), and TEA (4.43 mL, 31.8 mmol) to yield methyl 1-tert-butyl-5-methyl-1H-pyrazole-4-carboxylate after chromatography using a 80-g SiO2 pre-packed column eluting with 0:1-3:7 EtOAc/heptane. Said product was used directly in the next step without further purification. 1H-NMR (400 MHz, CDCl3) δ: 7.78 (s, 1H), 3.80 (s, 3H), 2.75 (s, 3H), 1.66 (s, 9H).

Sources & evidence

ORD record
ord-e76f390d38be4805aa64720d9e8ff6ec
Source dataset
uspto-grants-2015_05
Patent number
US09023846B2

Reaction notes

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