3-Pyridinecarboxaldehyde → Trans-(4,5-dihydro-5-(pyridin-3-yl)oxazol-4-yl)(pyrrolidin-1-yl)methanone

HRID 469699Notes

Reaction equation

HRID 469699 reaction equation
[OH-].[K+].[N:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH:9]=[O:10])[CH:4]=1.[N+:11]([CH2:13][C:14]([N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)=[O:15])#[C-:12]>CO>[N:3]1[CH:8]=[CH:7][CH:6]=[C:5]([C@@H:9]2[O:10][CH:12]=[N:11][C@H:13]2[C:14]([N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:15])[CH:4]=1

Participants

5

Reactant 3

HCID 103713-PyridinecarboxaldehydeHCID 14797Potassium HydroxideHCID 6455476Pyrrolidine, 1-(isocyanoacetyl)-

Product 1

HCID 66901556Trans-(4,5-dihydro-5-(pyridin-3-yl)oxazol-4-yl)(pyrrolidin-1-yl)methanoneYield 39%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred and cooled (0° C.) solution of potassium hydroxide (0.55 g, 9.80 mmol) in methanol (10 mL) were added a mixture of 3-pyridine carboxaldehyde (1.03 mL, 10.84 mmol) and 2-isocyano-1-(pyrrolidin-1-yl)ethanone BLE 04098 (1.50 g, 10.86 mmol). The solution was stirred 3 h at 0° C. and then concentrated. The residue was partitioned between ethyl acetate (100 mL) and water. The organic layer was combined with two additional ethyl acetate extracts (2×100 mL), washed with aqueous sodium chloride and dried over MgSO4, filtered and evaporated. Concentration afforded a crude product which was purified by column chromatography on silica (CH2Cl2:MeOH=98:2) to yield to trans-(4,5-dihydro-5-(pyridin-3-yl)oxazol-4-yl)(pyrrolidin-1-yl)methanone BLE 04110B (0.95 g, 39%) as a pale yellow pale solid.

Workup

  1. additionwere added
  2. stirringThe solution was stirred 3 h at 0° C.
  3. concentrationconcentrated
  4. customThe residue was partitioned between ethyl acetate (100 mL) and water
  5. washwashed with aqueous sodium chloride
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. concentrationConcentration
  10. customafforded a crude product which
  11. customwas purified by column chromatography on silica (CH2Cl2:MeOH=98:2)

Sources & evidence

ORD record
ord-ebcc10b6cfcb43b0903e346a8e039040
Source dataset
uspto-grants-2014_01
Patent number
US08629165B2

Reaction notes

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