Sodium Bicarbonate → Methyl 2-(3-Chloro-2-pyridyl)-5-oxopyrazolidine-3-carboxylate

HRID 1173543Notes

Reaction equation

HRID 1173543 reaction equation
Br[CH:2]([CH2:7][C:8](Cl)=[O:9])[C:3]([O:5][CH3:6])=[O:4].[Cl:11][C:12]1[C:13](=[N:18][NH2:19])[NH:14][CH:15]=[CH:16][CH:17]=1.C(=O)(O)[O-].[Na+]>C(#N)C>[Cl:11][C:12]1[C:13]([N:18]2[CH:2]([C:3]([O:5][CH3:6])=[O:4])[CH2:7][C:8](=[O:9])[NH:19]2)=[N:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5561003-Chloro-2-hydrazinylpyridineHCID 11390578Methyl 2-bromo-4-chloro4-oxobutanoateHCID 178514363HCID 178514363, compound

Product 1

HCID 11425364Methyl 2-(3-Chloro-2-pyridyl)-5-oxopyrazolidine-3-carboxylateYield 89.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

The crude product of Step B (i.e. methyl 2-bromo-4-chloro-4-oxobutanoate) (11.00 g, ˜47.4 mmol) in acetonitrile (25 mL) was added over 65 minutes to a mixture of 3-chloro-2(1H)-pyridinone hydrazone (alternatively named (3-chloro-pyridin-2-yl)-hydrazine) (6.55 g, 45.6 mmol) and sodium bicarbonate (9.23 g, 0.110 mol) in acetonitrile (60 mL) at 0° C. The mixture was then allowed to warm to room temperature and was stirred for 3 h. The mixture was then warmed and maintained at 38° C. for 8 h. Then the mixture was allowed to cool, and the solvent was removed by evaporation under reduced pressure. Water (25 mL) was added, and acetic acid (about 1.9 mL) was added until the slurry had a pH of about 5. After 2 h, the product was isolated by filtration, rinsed with water (10 mL) and dried in vacuo to provide the title compound as a pale yellow solid (11 g, 89.8% yield). A sample recrystallized from ethanol melted at 147-148° C.

Workup

  1. temperatureThe mixture was then warmed
  2. temperaturemaintained at 38° C. for 8 h
  3. temperatureto cool
  4. customthe solvent was removed by evaporation under reduced pressure
  5. additionWater (25 mL) was added
  6. additionacetic acid (about 1.9 mL) was added until the slurry
  7. waitAfter 2 h
  8. customthe product was isolated by filtration
  9. washrinsed with water (10 mL)
  10. customdried in vacuo

Sources & evidence

ORD record
ord-11305372bf98425c9c27647b6be38084
Source dataset
uspto-grants-2010_11
Patent number
US07834186B2

Reaction notes

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