Methyl Acrylate → Methyl 3-chloro-1-(pyridine-3-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate

HRID 512730Notes

Reaction equation

HRID 512730 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([NH:8]/[N:9]=[CH:10]/[C:11](O)=O)[CH:3]=1.[Cl:14]N1C(=O)CCC1=O.[C:22]([O:26][CH3:27])(=[O:25])[CH:23]=C.C(=O)(O)[O-].[K+].C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.O>[Cl:14][C:10]1[CH2:11][CH:23]([C:22]([O:26][CH3:27])=[O:25])[N:8]([C:4]2[CH:3]=[N:2][CH:7]=[CH:6][CH:5]=2)[N:9]=1

Participants

8

Reactant 5

HCID 7294Methyl AcrylateHCID 10340Sodium CarbonateHCID 31398ChlorosuccinimideHCID 516893Potassium BicarbonateHCID 118022438(2E)-2-(pyridin-3-ylhydrazinylidene)acetic acid;hydrochloride

Product 1

HCID 118022669Methyl 3-chloro-1-(pyridine-3-yl)-4,5-dihydro-1H-pyrazole-5-carboxylateYield 65.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

(E)-2-(2-(Pyridin-3-yl)hydrazono)acetic acid hydrochloride (13.6 g, 64.1 mmol) was stirred in ethyl acetate (250 mL). N-chlorosuccinimide (17.9 g, 131 mmol) was added and the reaction stirred for 10 minutes. Methyl acrylate (35.2 mL, 385 mmol) was added followed by addition of potassium bicarbonate (19.4 g, 192 mmol). Water (0.05 mL) was added and the mixture stirred at 18° C. The reaction temperature rose from 18 to 21° C. over 1 hour and the reaction was stirred for 20 hours. Water (300 mL) and saturated aqueous sodium carbonate (˜100 mL) were added. The mixture was filtered through Celite® and the filtrate was extracted with ethyl acetate (2×500 mL). The organic layers were dried and concentrated. The residue was purified by flash column chromatography using 50-100% ethyl acetate/hexanes as eluent to afford the desired product as an orange oil (10.1 g, 62.5%): 1H NMR (400 MHz, CDCl3) δ 8.30 (dd, J=2.9, 0.7 Hz, 1H), 8.18 (dd, J=4.7, 1.4 Hz, 1H), 7.38 (ddd, J=8.4, 2.9, 1.4 Hz, 1H), 7.19 (ddd, J=8.5, 4.7, 0.7 Hz, 1H), 4.81 (dd, J=12.4, 6.9 Hz, 1H), 3.79 (s, 3H), 3.56 (dd, J=17.8, 12.4 Hz, 1H), 3.34 (dd, J=17.8, 6.9 Hz, 1H); ESIMS m/z 240 ([M+H]+).

Workup

  1. stirringthe mixture stirred at 18° C
  2. waitThe reaction temperature rose from 18 to 21° C. over 1 hour
  3. stirringthe reaction was stirred for 20 hours
  4. filtrationThe mixture was filtered through Celite®
  5. extractionthe filtrate was extracted with ethyl acetate (2×500 mL)
  6. customThe organic layers were dried
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-518e8be8bc1249ac8d4b1ced179a4bbe
Source dataset
uspto-grants-2015_08
Patent number
US09102654B2

Reaction notes

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