Pyridine → [5-(1-Methyl-cyclopropyl)-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester

HRID 1993676Notes

Reaction equation

HRID 1993676 reaction equation
[Cl:1][C:2]([Cl:9])([Cl:8])[CH2:3][O:4][C:5](Cl)=[O:6].F[C:11](F)(F)[C:12]1([C:15]2[CH:16]=[C:17]([NH2:27])[N:18]([C:20]3[CH:25]=[CH:24][C:23]([CH3:26])=C[CH:21]=3)[N:19]=2)[CH2:14][CH2:13]1.[N:30]1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C1COCC1.ClCCl>[Cl:1][C:2]([Cl:9])([Cl:8])[CH2:3][O:4][C:5](=[O:6])[NH:27][C:17]1[N:18]([C:20]2[CH:21]=[N:30][C:23]([CH3:26])=[CH:24][CH:25]=2)[N:19]=[C:15]([C:12]2([CH3:11])[CH2:13][CH2:14]2)[CH:16]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 870632,2,2-Trichloroethyl chloroformateHCID 516892Sodium BicarbonateHCID 668765651-p-tolyl-3-(1-(trifluoromethyl)cyclopropyl)-1H-pyrazol-5-amine

Product 1

HCID 68538118[5-(1-Methyl-cyclopropyl)-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl esterYield 75.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-15 °C

Procedure

Add a solution of 2,2,2-trichloroethylchloroformate (1.80 g, 8.5 mmol) in THF (10 mL) dropwise to an ice-salt cooled solution of 5-(1-trifluoromethyl-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-ylamine (2.29 g, 8.1 mmol) and pyridine (0.9 mL, 11 mmol) in THF (30 mL) at −15° C. Stir at −15° C. for 0.5 hours and then 22° C. for 1 hour, then distribute the reaction mixture between dichloromethane (50 mL) and a saturated aq. sodium bicarbonate solution (50 mL). Isolate the aqueous phase and extract twice with dichloromethane (25 mL each). Dry the combined organic phases over sodium sulfate and concentrate. Subject residue to silica gel chromatography eluting with hexanes and ethyl acetate to give a white solid (2.46 g, 66% yield). MS(ES+): m/z=457.2 [M+H].

Workup

  1. wait22° C. for 1 hour
  2. customIsolate the aqueous phase
  3. extractionextract twice with dichloromethane (25 mL each)
  4. dry with materialDry the combined organic phases over sodium sulfate
  5. concentrationconcentrate
  6. washSubject residue to silica gel chromatography eluting with hexanes and ethyl acetate

Sources & evidence

ORD record
ord-984b9d82af544506a7f3a2f375157f9f
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

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