Ethyl 3-ethoxy-3-iminopropionate hydrochloride → HCID 15751497, compound

HRID 1974624Notes

Reaction equation

HRID 1974624 reaction equation
[CH:1]1([NH:4][C:5]2[C:6]([N+:25]([O-])=O)=[CH:7][C:8]([F:24])=[C:9]([N:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[CH:10]=2)[CH2:3][CH2:2]1.[H][H].Cl.C(O[C:34](=N)[CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])C>CO.[Pd]>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][N:11]([C:9]2[C:8]([F:24])=[CH:7][C:6]3[N:25]=[C:34]([CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])[N:4]([CH:1]4[CH2:2][CH2:3]4)[C:5]=3[CH:10]=2)[CH2:12][CH2:13]1)=[O:18])([CH3:22])([CH3:23])[CH3:21]

Participants

6

Reactant 3

HCID 75345Ethyl 3-ethoxy-3-iminopropionate hydrochlorideHCID 15751487HCID 15751487, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 15751497HCID 15751497, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

tert-Butyl 4-[5-(cyclopropylamino)-2-fluoro-4-nitrophenyl]-1-piperazinecarboxylate (17.21 g, 45.2 mmol) is dissolved in methanol (500 ml) and hydrogenated with 5 percent Pd/C (500 mg) under hydrogen at normal pressure. The hydrogen uptake amounts to 3.04 l. The palladium/carbon is filtered off under an inert gas and the methanol is distilled off under reduced pressure. The residue is dried in a high vacuum, then dissolved in DMF (150 ml) and treated with ethyl 3-ethoxy-3-iminopropanoate hydrochloride (17.3 g, 88.4 mmol). The solution obtained is heated to 50° for 2 hours. The DMF is distilled off, the residue is dissolved in water and the pH is adjusted to 8.0 with saturated sodium bicarbonate solution. The solution is extracted with ethyl acetate and the organic phase is washed in succession with water, 10 percent sodium chloride solution and then dried over magnesium sulfate. The solution is evaporated under reduced pressure and the residue is chromatographed on silica gel (eluent:ethyl acetate). The product is then recrystallized from ethyl acetate/hexane. There are obtained 15.5 g (78%) of ethyl 6-[4-(tert-butoxycarbonyl)-1-piperazinyl]-1-cyclopropyl-5-fluoro-2-benzimidazoleacetate with a m.p. of 152°-153°.

Workup

  1. filtrationThe palladium/carbon is filtered off under an inert gas
  2. distillationthe methanol is distilled off under reduced pressure
  3. customThe residue is dried in a high vacuum
  4. dissolutiondissolved in DMF (150 ml)
  5. customThe solution obtained
  6. temperatureis heated to 50° for 2 hours
  7. distillationThe DMF is distilled off
  8. dissolutionthe residue is dissolved in water
  9. extractionThe solution is extracted with ethyl acetate
  10. washthe organic phase is washed in succession with water, 10 percent sodium chloride solution
  11. dry with materialdried over magnesium sulfate
  12. customThe solution is evaporated under reduced pressure
  13. customthe residue is chromatographed on silica gel (eluent:ethyl acetate)
  14. customThe product is then recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-cd072a1d87864f72b38ef365b9feded8
Source dataset
uspto-grants-1994_02
Patent number
US05283248

Reaction notes

Loading…