Cyclopropylamine → 3-Benzyloxy-1-cyclopropyl-6-methyl-4-oxo-1,4-dihydro-pyridine-2-carboxylic acid

HRID 420478Notes

Reaction equation

HRID 420478 reaction equation
[CH2:1]([O:8][C:9]1[C:14](=[O:15])[CH:13]=[C:12]([CH3:16])O[C:10]=1[C:17]([OH:19])=[O:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:20]1([NH2:23])[CH2:22][CH2:21]1>CO>[CH2:1]([O:8][C:9]1[C:14](=[O:15])[CH:13]=[C:12]([CH3:16])[N:23]([CH:20]2[CH2:22][CH2:21]2)[C:10]=1[C:17]([OH:19])=[O:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 69828CyclopropylamineHCID 98564973-(benzyloxy)-6-methyl-4-oxo-4H-pyran-2-carboxylic acid

Product 1

HCID 666589263-Benzyloxy-1-cyclopropyl-6-methyl-4-oxo-1,4-dihydro-pyridine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 3-(benzyloxy)-6-methyl-4-oxo-4H-pyran-2-carboxylic acid (70 g, 0.27 mol) in MeOH (350 mL) in a 3-necked RBF (round bottom flask) fitted with a mechanical stirrer was added cyclopropylamine (120 mL, 1.72 mol). A clear light yellow solution resulted. The reaction mixture was refluxed for ca. 19 h. Volatiles were removed in vacuo and the residue was dissolved in water (700 mL) with stirring. The aqueous mixture was filtered through a pad of Celite®. The filtrate was placed in a 3-necked RBF fitted with a mechanical stirrer, and cooled in an ice bath. Conc. HCl was added until the pH was ca. 1-2, and voluminous “orange” solid precipitated out. Acetone (200 mL) was added to the suspension. The solid was then collected by suction filtration, thoroughly washed with acetone, and air-dried. The title compound was obtained as an off-white solid (71.0 g, 88%). Mp: 139.0-139.5° C.; 1H-NMR (300 MHz, DMSO-D6) δ (ppm): 0.98-1.15 (m, 4H, 2 c-CH2), [2.37 (s)+2.40 (s), rotamers, 3/2 ratio, 3H, CH3)], 3.30-3.50 (m, 1H, c-CH), 5.00-5.05 (m, 2H, CH2Ph), 6.20-6.25 (m, 1H, C═CH), 7.28-7.50 (m, 5H, Ph); MS (m/z): 300.2 (M++1), 256.2, 192.2, 164.4, 91.0 (100%); Anal. Calcd. for C17H17NO4: C, 68.21; H, 5.72; N, 4.68%. Found: C, 67.76; H, 5.76; N, 4.61%.

Workup

  1. customfitted with a mechanical stirrer
  2. customA clear light yellow solution resulted
  3. temperatureThe reaction mixture was refluxed for ca. 19 h
  4. customVolatiles were removed in vacuo
  5. dissolutionthe residue was dissolved in water (700 mL)
  6. filtrationThe aqueous mixture was filtered through a pad of Celite®
  7. customfitted with a mechanical stirrer
  8. temperaturecooled in an ice bath
  9. additionConc. HCl was added until the pH was ca. 1-2, and voluminous “orange” solid
  10. customprecipitated out
  11. additionAcetone (200 mL) was added to the suspension
  12. filtrationThe solid was then collected by suction filtration
  13. washthoroughly washed with acetone
  14. customair-dried

Sources & evidence

ORD record
ord-57aff80f53664037b499128f9852872b
Source dataset
uspto-grants-2012_01
Patent number
US08097624B2

Reaction notes

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