Hydrochloric Acid → HCID 178472189, compound

HRID 1935720Notes

Reaction equation

HRID 1935720 reaction equation
[Cl-].[Mg+2].[Cl-].C(C(C([O-])=O)C([O-])=O)C.[K+].[K+].C(N1C=CN=C1)(N1C=CN=C1)=O.[Si:27]([O:34][C:35]1[CH:36]=[C:37](C(O)=O)[C:38]2[NH:42][C:41]([CH2:43][CH2:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)=[N:40][C:39]=2[CH:51]=1)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28].[Mg+2].[C:56]([O:62][CH2:63][CH3:64])(=[O:61])[CH2:57][C:58]([O-])=[O:59].C(OC(=O)CC([O-])=O)C.Cl.C(=O)(O)[O-].[Na+]>O1CCCC1.C(#N)C.C(N(CC)CC)C>[Si:27]([O:34][C:35]1[CH:36]=[C:37]([C:58](=[O:59])[CH2:57][C:56]([O:62][CH2:63][CH3:64])=[O:61])[C:38]2[NH:42][C:41]([CH2:43][CH2:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)=[N:40][C:39]=2[CH:51]=1)([C:30]([CH3:32])([CH3:33])[CH3:31])([CH3:29])[CH3:28]

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 516892Sodium BicarbonateHCID 5360315Magnesium ChlorideHCID 11066066CID 11066066HCID 86617294Potassium ethylmalonateHCID 178455074HCID 178455074, compound

Product 1

HCID 178472189HCID 178472189, compound

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

Triethylamine (2.65 mL) and magnesium chloride (2.16 g) were added to dry acetonitrile (37.5 mL) suspension of potassium ethylmalonate (3.23 g), and the mixture was vigorously stirred at room temperature for 16 hours under in an atmosphere of argon. Next, a catalytically effective amount of N,N-dimethylaminopyridine and 1,1′-carbonyldiimidazole (1.35 g) were added to anhydrous tetrahydrofuran (30 mL) solution of 6-t-butyldimethylsilyloxy-2-(2-phenylethyl)benzimidazole-4-carboxylic acid (3.0 g) obtained in Reference Example 23, and the mixture was stirred for 1 hour under an atmosphere of argon. This was diluted to the previously prepared suspension of ethyl malonate magnesium salt while cooling in an ice bath, and the mixture was stirred at room temperature for 2 hours. This was diluted with ice water (50 mL) and, while cooling in an ice bath, adjusted to pH 1 with 4 N hydrochloric acid. While cooling in an ice bath, this was adjusted to pH 8 to 9 with saturated sodium bicarbonate aqueous solution and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate, and then the solvent was evaporated under a reduced pressure. The resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) and the desired fraction was concentrated to obtain the title compound as colorless oil (3.44 g).

Workup

  1. customobtained in Reference Example 23
  2. stirringthe mixture was stirred for 1 hour under an atmosphere of argon
  3. temperaturewhile cooling in an ice bath
  4. stirringthe mixture was stirred at room temperature for 2 hours
  5. temperaturewhile cooling in an ice bath
  6. temperatureWhile cooling in an ice bath
  7. extractionextracted with ethyl acetate
  8. washThe organic layer was washed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. customthe solvent was evaporated under a reduced pressure
  11. customThe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)
  12. concentrationthe desired fraction was concentrated

Sources & evidence

ORD record
ord-84d5264c86304383ae038132edb427cf
Source dataset
uspto-grants-2002_05
Patent number
US06387938B1

Reaction notes

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