Methyl formate → Methyl 2-formyl-3-(pyrimidin-5-yl)propanoate

HRID 705789Notes

Reaction equation

HRID 705789 reaction equation
CC([O-])(C)C.[K+].[CH:7]([O:9][CH3:10])=[O:8].[N:11]1[CH:16]=[C:15]([CH2:17][CH2:18][C:19](OC)=[O:20])[CH:14]=[N:13][CH:12]=1>C1COCC1>[CH:19]([CH:18]([CH2:17][C:15]1[CH:16]=[N:11][CH:12]=[N:13][CH:14]=1)[C:7]([O:9][CH3:10])=[O:8])=[O:20]

Participants

5

Reactant 3

HCID 7865Methyl formateHCID 18470121Methyl 3-(pyrimidin-5-yl)propanoateHCID 23665647Potassium tert-butoxide

Product 1

HCID 86666186Methyl 2-formyl-3-(pyrimidin-5-yl)propanoateYield 60.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To an ice-cooled solution of KOtBu (43.0 g, 384 mmol) in anhydrous THF (300 ml) stirred under nitrogen was added methyl formate (18.43 g, 307 mmol) and methyl 3-(pyrimidin-5-yl)propanoate (25.5 g, 153 mmol) in anhydrous THF (10 mL) dropwise for 1 h. The mixture was stirred for 3 hr. The solvent was removed, and the residue was dissolved in water (150 mL). The aqueous phase was washed with ether (200 mL×3), and then to the aqueous solution was added AcOH to adjust the pH=5. The solid was collected and dried to give the target compound. The filtrate was extracted with DCM (200 mL×2), and the combined organic phase was dried over sodium sulfate, filtered and concentrated. The two crops were combined to give the title product as a yellow solid (18 g, 57.4% yield). LCMS: rt=0.96 min, [M+H+]=195

Workup

  1. stirringThe mixture was stirred for 3 hr
  2. customThe solvent was removed
  3. dissolutionthe residue was dissolved in water (150 mL)
  4. washThe aqueous phase was washed with ether (200 mL×3)
  5. additionto the aqueous solution was added AcOH
  6. customThe solid was collected
  7. customdried
  8. customto give the target compound
  9. extractionThe filtrate was extracted with DCM (200 mL×2)
  10. dry with materialthe combined organic phase was dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-dc04e54d676c4bbfabf0ab621264595c
Source dataset
uspto-grants-2015_11
Patent number
US09174968B2

Reaction notes

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