Water → Ethyl 1-(5-fluoropyridin-2-yl)piperidine-4-carboxylate

HRID 587393Notes

Reaction equation

HRID 587393 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.[NH:9]1[CH2:19][CH2:18][CH:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:11][CH2:10]1.CCN(C(C)C)C(C)C.O>CN1C(=O)CCC1>[CH2:16]([O:15][C:13]([CH:12]1[CH2:18][CH2:19][N:9]([C:2]2[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=2)[CH2:10][CH2:11]1)=[O:14])[CH3:17]

Participants

6

Reactant 4

HCID 962WaterHCID 70770Ethyl 4-piperidinecarboxylateHCID 81531DiisopropylethylamineHCID 27831712-Bromo-5-fluoropyridine

Product 1

HCID 58302994Ethyl 1-(5-fluoropyridin-2-yl)piperidine-4-carboxylateYield 30%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 3.4 g (20 mmol) 2-bromo-5-fluoropyridine, 4.61 g (29 mmol) ethyl isonipecotate and 3.79 g (29 mmol) DIPEA in 5 mL NMP was heated for 15 min to 170° C. and 60 min to 200° C. After cooling to room temperature water was added and the mixture was extracted with ethyl acetate and heptane. The combined organic layers were washed with brine, dried with Na2SO4, filtered and evaporated to dryness. The residue was purified by column chromatography on silica eluting with a gradient formed from heptane and ethyl acetate. The product containing fractions were evaporated to yield 1.5 g (30%) of the title compound as light yellow oil. MS m/e: 253.3 [M]+.

Workup

  1. temperaturewas heated for 15 min to 170° C. and 60 min to 200° C
  2. additionwas added
  3. extractionthe mixture was extracted with ethyl acetate and heptane
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe residue was purified by column chromatography on silica eluting with a gradient
  9. customformed from heptane and ethyl acetate
  10. additionThe product containing fractions
  11. customwere evaporated

Sources & evidence

ORD record
ord-050d18afa9674a5abddf121a55194338
Source dataset
uspto-grants-2016_01
Patent number
US09226916B2

Reaction notes

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