Hydrochloric Acid → HCID 20079405, compound

HRID 256879Notes

Reaction equation

HRID 256879 reaction equation
C([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)(OC)=O.[CH3:19]C(C)([O-])C.[K+].Cl>C1(C)C=CC=CC=1>[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:13][CH3:14])=[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-carbomethoxymethyl-trans-3,4-dicarbomethoxypyrrolidine (5 g, 19.31 mmol) in toluene (75 ml) was added dropwise over a 1 h 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 h, cooled to room temperature and concentrated hydrochloric acid (75 ml) added dropwise and stirred for 0.25 h. The organic phase was extracted with further portions of acid (3×50 ml) and the combined aqueous heated at 110° C. for 16 h. The solvent was then removed under vacuum, the residue dried and taken up into methanol (saturated with hydrogen chloride) (150 ml). The mixture was stirred at room temperature for 24 h 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 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. (isopropylalcohol); (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=3 and 9.8 Hz, CH of CH2 --N); 2.63 (1H, dd, J=3 and 12.7 Hz, CH of CH2 --N); 2.77 (1H, d, J=12.7 Hz, CH of CH2 --N); 2.80-3.10 (5H, m, 2 of CH and 1.5 of CH2); 3.11 (3H, s, OMe); 3.24 (3H, s, OMe); 3.71 (3H, s, CO2Me).

Workup

  1. temperatureThe mixture was refluxed for 4 h
  2. extractionThe organic phase was extracted with further portions of acid (3×50 ml)
  3. temperaturethe combined aqueous heated at 110° C. for 16 h
  4. customThe solvent was then removed under vacuum
  5. customthe residue dried
  6. stirringThe mixture was stirred at room temperature for 24 h
  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 solvents
  12. customwas chromatographed through silica-gel

Sources & evidence

ORD record
ord-64c7e73f58e24ad29b5ff248e3d00999
Source dataset
uspto-grants-1993_11
Patent number
US05260293

Reaction notes

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