Water → Methyl 2-Chloro-5-fluoro-6-pyrrolidin-1-ylnicotinate

HRID 385590Notes

Reaction equation

HRID 385590 reaction equation
[Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]([F:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[NH:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1.C(OCC)(=O)C.O>CN(C)C=O.C(N(CC)CC)C>[Cl:1][C:2]1[N:11]=[C:10]([N:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[C:9]([F:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 31268Pyrrolidine2×HCID 2775354Methyl 2,6-dichloro-5-fluoronicotinate

Product 1

HCID 57815196Methyl 2-Chloro-5-fluoro-6-pyrrolidin-1-ylnicotinate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 1.5 g of methyl 2,6-dichloro-5-fluoronicotinate in 15 mL of N,N-dimethylformamide, 0.93 mL of triethylamine was added at room temperature, and thereto was dropped 0.56 mL of pyrrolidine. The mixture was stirred at the same temperature for 1 hour, 56 μL of pyrrolidine was further added, and the mixture was stirred for 50 minutes. After leaving overnight, ethyl acetate and water were added to the reaction mixture. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed with water and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 1.7 g of methyl 2-chloro-5-fluoro-6-(pyrrolidin-1-yl)nicotinate as a white solid.

Workup

  1. stirringthe mixture was stirred for 50 minutes
  2. customAfter leaving overnight
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washthe resultant solution was washed with water
  6. dry with materiala saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-802794bf4c0443209da51c2920b6b611
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

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