Chlorobenzene → Isopyrazam

HRID 1193010Notes

Reaction equation

HRID 1193010 reaction equation
[CH3:1][C:2]([CH3:5])([O-])[CH3:3].[K+].C(O[C:10]([C:12]1[C:13]([CH:18]([F:20])[F:19])=[N:14][N:15]([CH3:17])[CH:16]=1)=[O:11])C.Cl[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>>[CH:2]([CH:5]1[CH:23]2[C:22]3[C:27]([CH:26]1[CH2:25][CH2:24]2)=[CH:18][CH:13]=[CH:12][C:16]=3[NH:15][C:10]([C:12]1[C:13]([CH:18]([F:19])[F:20])=[N:14][N:15]([CH3:17])[CH:16]=1)=[O:11])([CH3:3])[CH3:1]

Participants

4

Reactant 3

HCID 7964ChlorobenzeneHCID 11644126Ethyl 3-difluoromethyl-1-methyl-4-pyrazole carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 25271089Isopyrazam

Conditions

Temperature
95 °C

Procedure

6.2 g of 9-isopropyl-5-amino-benzonorbornene (Comp. No. Z3.11, syn/anti ratio 90:10; mmol, 1.05 equivalents) and 1.6 g of potassium tert-butoxide (14.7 mmol, 0.5 equivalent) are added to a solution of 6 g of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (29 mmol) in 60 ml of chlorobenzene. The reaction mixture is heated to 95° C. and the chlorobenzene solvent is completely removed in vacuo. The reaction mixture is heated to 120° C. and stirred for 20 hours. 30 ml of chlorobenzene are then added. The organic phase is extracted twice with water, first at low pH, then at high pH. The organic phase is concentrated by distilling off chlorobenzene. 8 g of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (9-isopropyl-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-yl)-amide are obtained in the form of a brown oil (crude yield: 33%).

Workup

  1. customthe chlorobenzene solvent is completely removed in vacuo
  2. temperatureThe reaction mixture is heated to 120° C.
  3. addition30 ml of chlorobenzene are then added
  4. extractionThe organic phase is extracted twice with water, first at low pH
  5. concentrationThe organic phase is concentrated
  6. distillationby distilling off chlorobenzene

Sources & evidence

ORD record
ord-c013c1ed2c3b4c7a8e8d030056c99822
Source dataset
uspto-grants-2014_03
Patent number
US08680337B2

Reaction notes

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