Hydrochloric Acid → HCID 178471175, compound

HRID 412722Notes

Reaction equation

HRID 412722 reaction equation
Cl.Cl.[NH:3]1[C:11]2[CH2:10][CH2:9][NH:8][CH2:7][C:6]=2[N:5]=[C:4]1[CH:12]([CH3:18])[C:13]([O:15][CH2:16][CH3:17])=[O:14].C(N(CC)C(C)C)(C)C.Cl[C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30].[O-]CC.[Na+].Cl>C(#N)C>[CH2:16]([O:15][C:13]([CH:12]([C:4]1[NH:3][C:11]2[CH2:10][CH2:9][N:8]([C:29]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[O:30])[CH2:7][C:6]=2[N:5]=1)[CH3:18])=[O:14])[CH3:17]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 10387Benzyl chloroformateHCID 81531Diisopropylethylamine2×HCID 2723922Sodium ethoxideHCID 178471174HCID 178471174, compound

Product 1

HCID 178471175HCID 178471175, compoundYield 72.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A solution comprising ethyl 2-(4,5,6,7-tetrahydroimidazo[4,5-c]pyridin-2-yl)propionate dihydrochloride (60.2 g, 0.20 mol) in acetonitrile (400 mL) was cooled to 0° C. under nitrogen, treated with N,N-diisopropylethylamine (35 mL, 0.20 mol), further cooled to ˜−5° C. (ice/acetone) and then treated with benzyl chloroformate (58 mL, 0.41 mol) and N,N-diisopropylethylamine (70 mL, 0.40 mol) in alternating portions over 30 minutes. The mixture was cooled at −5° C. for 1 hour and allowed to warm to 20° C. and, after 16 hours, concentrated under reduced pressure. The residue was suspended in ether and the suspension was washed successively with sodium bicarbonate, sodium chloride, 0.1M hydrochloric acid and sodium chloride, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was dissolved in ethanol (320 mL) and the solution was cooled to −5° C. under nitrogen and then sodium ethoxide (21 wt %, 85 mL, 0.22 mol) was added dropwise over 1 hour while the reaction temperature was maintained below 0° C. The mixture was cooled at −5° C. for 1 hour, adjusted to neutral pH with 50 mL of 4M hydrochloric acid and concentrated under reduced pressure. The residue was dissolved in ethyl acetate and the solution was washed with sodium bicarbonate and sodium chloride, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexanes/ethyl acetate) to provide benzyl 2-(1-ethoxycarbonylethyl)-1,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylate (52 g, 72%) as a pale yellow oil; 1H-NMR (300 MHz, DMSO-d6) d ppm: 11.72 (br s, 1H), 7.32 (s, 5H), 5.07 (s, 2H), 4.32 (br s, 2H), 4.02 (q, 2H, J=9.3 Hz), 3.77 (q, 1H, J=8.3 Hz), 3.66 (s, 2H), 2.55 (s, 2H), 1.38 (d, 3H, J=8.3 Hz), 1.13 (t, 3H, J=9.3 Hz).

Workup

  1. customover 30 minutes
  2. temperatureThe mixture was cooled at −5° C. for 1 hour
  3. temperatureto warm to 20° C. and, after 16 hours
  4. concentrationconcentrated under reduced pressure
  5. washthe suspension was washed successively with sodium bicarbonate, sodium chloride, 0.1M hydrochloric acid and sodium chloride
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe residue was dissolved in ethanol (320 mL)
  10. temperaturethe solution was cooled to −5° C. under nitrogen
  11. temperaturewas maintained below 0° C
  12. temperatureThe mixture was cooled at −5° C. for 1 hour
  13. concentrationconcentrated under reduced pressure
  14. dissolutionThe residue was dissolved in ethyl acetate
  15. washthe solution was washed with sodium bicarbonate and sodium chloride
  16. dry with materialdried (Na2SO4)
  17. filtrationfiltered
  18. concentrationconcentrated under reduced pressure
  19. customThe residue was purified by silica gel chromatography (hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-b3bc47b7816746a18bec4805e1b388d8
Source dataset
uspto-grants-2003_05
Patent number
US06562854B2

Reaction notes

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