Ethyl formate → 4-cyclopropyl-1H-pyrazol-3-amine

HRID 528770

Reaction equation

HRID 528770 reaction equation
[Na].[CH:2](OCC)=O.[CH:7]1([CH2:10][C:11]#[N:12])[CH2:9][CH2:8]1.[NH2:13][NH2:14]>CCOCC.C1COCC1.C(O)(=O)C>[CH:7]1([C:10]2[CH:2]=[N:14][NH:13][C:11]=2[NH2:12])[CH2:9][CH2:8]1

Participants

8

Reactant 4

HCID 8025Ethyl formateHCID 9321HydrazineHCID 643447CyclopropylacetonitrileHCID 5360545Sodium

Product 1

HCID 235693104-cyclopropyl-1H-pyrazol-3-amine

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To 7 g (0.3 mol) of freshly cut sodium chunks in 220 mL dry ether under nitrogen and external ice cooling was added a solution of 25 mL (0.3 mol) ethyl formate followed by a solution of 25 g (0.3 mol) cyclopropylacetonitrile in 50 mL dry ether, and the mixture was stirred at room temperature for 2 days. 19 mL (0.3 mol) glacial acetic acid was added whilst maintaining the internal temperature at 10-12° C., the solids were filtered off and the filtrate was concentrated at below 20° C. The residue was treated with 300 mL (0.6 mol) 2 M hydrazine in THF, 5 mL glacial acetic acid and heated at reflux for 2 hours. After cooling, the mixture was concentrated and the desired product was obtained by kugelrohr distillation. The product was used in the next step without further purification.

Workup

  1. temperaturewhilst maintaining the internal temperature at 10-12° C.
  2. filtrationthe solids were filtered off
  3. concentrationthe filtrate was concentrated at below 20° C
  4. temperatureheated
  5. temperatureat reflux for 2 hours
  6. temperatureAfter cooling
  7. concentrationthe mixture was concentrated

Sources & evidence

ORD record
ord-68ba72dfd7d845bea27c13380b53b694
Source dataset
uspto-grants-2016_05
Patent number
US09346816B2

Linked notes

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