Sodium Hydroxide → 6-(1-(Tert-butoxycarbonyl)piperidin-4-yl)picolinic acid

HRID 385298Notes

Reaction equation

HRID 385298 reaction equation
C([O:3][C:4]([C:6]1[N:11]=[C:10]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)[CH:9]=[CH:8][CH:7]=1)=[O:5])C.[OH-].[Na+]>CO>[C:21]([O:20][C:18]([N:15]1[CH2:16][CH2:17][CH:12]([C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([C:4]([OH:5])=[O:3])[N:11]=2)[CH2:13][CH2:14]1)=[O:19])([CH3:24])([CH3:22])[CH3:23]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 66686619Ethyl 6-[1-(tert-butoxycarbonyl)piperidin-4-yl]pyridine-2-carboxylate

Product 1

HCID 666866476-(1-(Tert-butoxycarbonyl)piperidin-4-yl)picolinic acidYield 49%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-6,1′-dicarboxylic acid 1′-tert-butyl ester 6-ethyl ester (100 mg, 0.3 mmol) in methanol (5 mL) was added aq. solution of sodium hydroxide (2 M, 0.23 mL, 0.5 mmol) at RT. After stirring for 4 h at RT, the solvent was removed, and the residue was dissolved in THF (5 mL), and aq. solution of lithium hydroxide (7 mg in 1 mL of water) was added at RT. After stirring overnight at RT, the solvent was removed and the residue was dissolved in ethylacetate (10 mL) and the reaction mixture was acidified with 2M aq. solution of HCl until pH 2-3. After separation of phases, the aq. layer was re-extracted with ethylacetate (10 mL), and the combined organic layers were washed with brine (10 mL), dried over sodium sulfate, filtered, and evaporated under reduce pressure to give 3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-6,1′-dicarboxylic acid 1′-tert-butyl ester (45 mg, 49%), which can be used in the next step without further purification. 1H-NMR (400 MHz, d6-DMSO): δ=1.43 (s, 9H), 1.58-1.68 (m, 2H), 1.81-1.84 (m, 2H), 2.84-2.96 (m, 2H), 3.27-3.39 (m, 1H), 4.07-4.10 (m, 2H), 7.52-7.54 (d, 1H), 7.86-7.92 (m, 2H). MS: m/z=329 (M+23).

Workup

  1. customthe solvent was removed
  2. dissolutionthe residue was dissolved in THF (5 mL)
  3. additionaq. solution of lithium hydroxide (7 mg in 1 mL of water) was added at RT
  4. stirringAfter stirring overnight at RT
  5. customthe solvent was removed
  6. dissolutionthe residue was dissolved in ethylacetate (10 mL)
  7. customAfter separation of phases
  8. extractionthe aq. layer was re-extracted with ethylacetate (10 mL)
  9. washthe combined organic layers were washed with brine (10 mL)
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. customevaporated

Sources & evidence

ORD record
ord-a2815c8b33a84b52a355680f0c3bf062
Source dataset
uspto-grants-2013_02
Patent number
US08367844B2

Reaction notes

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