Acetic Acid → Methyl 4-methyl-1H-pyrazole-3-carboxylate

HRID 244614

Reaction equation

HRID 244614 reaction equation
[N+:1](=[CH2:3])=[N-:2].CC1C=CC(S(N(N=O)C)(=O)=O)=CC=1.[CH3:18][O:19][C:20](=[O:25])[C:21](Br)=[CH:22][CH3:23].C(O)(=O)C>C(OCC)C>[CH3:23][C:22]1[CH:3]=[N:1][NH:2][C:21]=1[C:20]([O:19][CH3:18])=[O:25]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6628DiazaldHCID 9550DiazomethaneHCID 87208Methyl-2-bromo-2-butenoate

Product 1

HCID 3467807Methyl 4-methyl-1H-pyrazole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of diazomethane (nominally 0.68 g—generated from DIAZALD® (5 g) in diethyl ether (45 ml)) at −78° C. was added a solution of E/Z methyl-2-bromo-2-butenoate (3.58 g) (available from Fluka) in diethyl ether (15 ml), dropwise, over 15 min. The mixture was maintained at −78° C. for 1 h then allowed to warm to 20° C. with stirring overnight. Acetic acid (1 ml) was added to destroy excess diazomethane and the mixture evaporated under reduced pressure. The residue was co-evaporated with toluene. Purification of the residue by column chromatography on silica gel eluting with ethyl acetate:cyclohexane (1:1) gave the title compound (1.12 g) as an orange solid.

Workup

  1. customat −78° C.
  2. temperatureto warm to 20° C.
  3. customto destroy excess diazomethane
  4. customthe mixture evaporated under reduced pressure
  5. customPurification of the residue by column chromatography on silica gel eluting with ethyl acetate:cyclohexane (1:1)

Sources & evidence

ORD record
ord-c95d3df20cc6468da6a8313315996ed5
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Linked notes

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