Hydrochloric Acid → HCID 20030818, compound

HRID 232031Notes

Reaction equation

HRID 232031 reaction equation
[CH3:1][C:2]1[N:3]([CH2:11][CH2:12][OH:13])[C:4]2[CH:9]=[CH:8][N:7]=[CH:6][C:5]=2[N:10]=1.[H-].[Na+].Cl[CH2:17][C:18](=[O:26])[CH2:19][C:20]([O:22][CH:23]([CH3:25])[CH3:24])=[O:21].Cl>O1CCCC1>[CH3:1][C:2]1[N:3]([CH2:11][CH2:12][O:13][CH2:17][C:18](=[O:26])[CH2:19][C:20]([O:22][CH:23]([CH3:25])[CH3:24])=[O:21])[C:4]2[CH:9]=[CH:8][N:7]=[CH:6][C:5]=2[N:10]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 2795580Isopropyl 4-chloroacetoacetateHCID 20030815HCID 20030815, compound

Product 1

HCID 20030818HCID 20030818, compoundYield 58.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2-Methyl-1-(2-hydroxyethyl)-imidazo[4,5-c]pyridine (5 g, 28.5 mmole) was added to a suspension of sodium hydride (60% oil dispersion, 2.3 g, 57 mmole) in dry tetrahydrofuran (100 ml) and the mixture was sonicated for 2 hours at room temperature. A solution of isopropyl 4-chloroacetoacetate (5.1 g, 28.5 mmole) in tetrahydrofuran (100 ml) was added dropwise under nitrogen with sonication and the mixture was sonicated for 5 hours at room temperature. 2N Hydrochloric acid (100 ml) was added and the tetrahydrofuran removed under reduced pressure. The aqueous solution was washed with methylene chloride (2×50 ml), neutralised with potassium carbonate and extracted with ethyl acetate (3×25 ml). The combined extracts were washed with water, dried over magnesium sulphate and evaporated. The residue was chromatographed on silica, eluting with ethyl acetate containing 10% isopropyl alcohol to yield isopropyl 4-[2-(2-methyl-1-imidazo[4,5-c]pyridyl)ethoxy]-3-ketobutanoate (5.3 g, 58%). Rf (silica; methanol, ethyl acetate 1:4) 0.13; N.M.R. (CDCl3) δ=1.05 (d, J=6 Hz, 6H); 2.50 (s, 3H); 3.15 (s, 2H); 3.67 (t, J=5.5 Hz, 2H); 3.93 (s, 2H); 4.19 (t, J=5.5 Hz, 2H); 4.8 (m, 1H); 7.11-8.19 (m, 3H).

Workup

  1. customthe mixture was sonicated for 2 hours at room temperature
  2. customthe mixture was sonicated for 5 hours at room temperature
  3. customthe tetrahydrofuran removed under reduced pressure
  4. washThe aqueous solution was washed with methylene chloride (2×50 ml)
  5. extractionextracted with ethyl acetate (3×25 ml)
  6. washThe combined extracts were washed with water
  7. dry with materialdried over magnesium sulphate
  8. customevaporated
  9. customThe residue was chromatographed on silica
  10. washeluting with ethyl acetate containing 10% isopropyl alcohol

Sources & evidence

ORD record
ord-322e89217ea54b66bc0f8d4036966a24
Source dataset
uspto-grants-1989_07
Patent number
US04851412

Reaction notes

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