Hydrochloric Acid → HCID 20079405, compound

HRID 1654101Notes

Reaction equation

HRID 1654101 reaction equation
COC([CH2:5][N:6]1[CH2:10][C@@H:9]([C:11]([O:13][CH3:14])=[O:12])[C@H:8]([C:15]([O:17][CH3:18])=[O:16])[CH2:7]1)=O.[CH3:19]C(C)([O-])C.[K+].Cl>C1(C)C=CC=CC=1>[CH3:14][O:13][C:11]([CH:9]1[CH:8]2[CH2:7][N:6]([CH2:5][C:15]2([O:16][CH3:19])[O:17][CH3:18])[CH2:10]1)=[O:12]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 23665647Potassium tert-butoxideHCID 67784567HCID 67784567, compound

Product 1

HCID 20079405HCID 20079405, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A solution of 1-methoxycarbonylmethyl-trans-3,4-dimethoxycarbonylpyrrolidine (5 g, 19.31 mmol) in toluene (75 ml) was added dropwise over a 1 hour period to a rapidly stirred solution of potassium-t-butoxide (9 g, 80 mmol) in toluene (250 ml) at 130° C. The mixture was refluxed for 4 hours, cooled to room temperature and concentrated hydrochloric acid (75 ml) added dropwise and stirred for 0.25 hours. The organic phase was extracted with further portions of hydrochloric acid (3×50 ml) and the combined aqueous heated at 110° C. for 16 hours. The solvent was then removed in vacuo, the residue dried and taken up into methanol (saturated with hydrogen chloride, 150 ml). The mixture was stirred at room temperature for 24 hours and the solvent removed under vacuum. The residue was dissolved in water (50 ml), basified to pH>10 with potassium carbonate and extracted with dichloromethane (5×150 ml). The combined extracts were dried (Na2SO4) and the residue remaining after removal of the solvents was chromatographed through silica-gel, using dichloromethane/methanol (93:7) as eluant, to give the title ester as a yellow liquid (0.5 g). An analytical sample was prepared as the hydrogen oxalate salt, mp 134.5°-136.5° C. (propan-2-ol); (Found: C, 47.04; H, 6.20; N, 4.50. C10H17NO4.(CO2H)2 requires C, 47.21; H, 6.27; N, 4.59%); δ (360 MHz, CDCl3) 2.44 (1H, dd, J=9.8 and 3.2 Hz), 2.63 (1H, dd, J=12.7 and 3.2 Hz), 2.77 (1H, d, J=12.7 Hz), 2.80-3.10 (5H, m), 3.11 (3H, s, OCH3), 3.24 (3H, s, OCH3), 3.71 (3H, s, CO2CH3).

Workup

  1. temperatureThe mixture was refluxed for 4 hours
  2. extractionThe organic phase was extracted with further portions of hydrochloric acid (3×50 ml)
  3. temperaturethe combined aqueous heated at 110° C. for 16 hours
  4. customThe solvent was then removed in vacuo
  5. customthe residue dried
  6. stirringThe mixture was stirred at room temperature for 24 hours
  7. customthe solvent removed under vacuum
  8. dissolutionThe residue was dissolved in water (50 ml)
  9. extractionextracted with dichloromethane (5×150 ml)
  10. dry with materialThe combined extracts were dried (Na2SO4)
  11. customafter removal of the solvents
  12. customwas chromatographed through silica-gel

Sources & evidence

ORD record
ord-644e942bc21e4b6ba3602dee6ddf8534
Source dataset
uspto-grants-1995_04
Patent number
US05405853

Reaction notes

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