Pyridine → [5-(1-Methoxy-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-yl]carbamic acid 2,2,2-trichloro-ethyl ester

HRID 729598Notes

Reaction equation

[CH3:1][O:2][C:3]1([C:6]2[CH:7]=[C:8]([NH2:18])[N:9]([C:11]3[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=3)[N:10]=2)[CH2:5][CH2:4]1.N1C=CC=CC=1.[Cl:25][C:26]([Cl:33])([Cl:32])[CH2:27][O:28][C:29](Cl)=[O:30]>C1COCC1>[Cl:25][C:26]([Cl:33])([Cl:32])[CH2:27][O:28][C:29](=[O:30])[NH:18][C:8]1[N:9]([C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)[N:10]=[C:6]([C:3]2([O:2][CH3:1])[CH2:5][CH2:4]2)[CH:7]=1

Participants

Conditions

Temperature: -15 °C

Procedure

To an ice-salt cooled solution of 5-(1-methoxy-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-ylamine (Preparation 11, 2.43 g, 10 mmol) and pyridine (0.9 mL, 11 mmol) in THF (30 mL), add a solution of 2,2,2-trichloroethylchloroformate (2.12 g, 10 mmol) in THF (10 mL) dropwise. Stir at −15° C. for 0.5 hour, then at 22° C. for 1 hour. Partition the reaction mixture between dichloromethane (50 mL) and saturated aq. sodium bicarbonate (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 (3.73 g, 89% yield, ES+(m/z) 418.1 [M+H]).

Workup

waitat 22° C. for 1 hour
customPartition the reaction mixture between dichloromethane (50 mL) and saturated aq. sodium bicarbonate (50 mL)
customIsolate the aqueous phase
extractionextract twice with dichloromethane (25 mL each)
dry with materialDry the combined organic phases over sodium sulfate
concentrationconcentrate
washSubject residue to silica gel chromatography eluting with hexanes and ethyl acetate
customto give a white solid (3.73 g, 89% yield, ES+(m/z) 418.1 [M+H])

Sources & evidence

ORD record: ord-1c0f4660d90c4e9a8523e9f28272863a
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07582638B2

Reaction notes

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