Pyridine → cis-(1R,2S)-2-(3-aminopropyl)-1-[1-(4-chlorophenyl)imidazol-4-yl]cyclopropane-1-carboxylic acid

HRID 1844579Notes

Reaction equation

HRID 1844579 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:7][C:8]1[CH:13]=[CH:12][C:11](B(O)O)=[CH:10][CH:9]=1.[C:17](=[O:20])(O)[O-:18].[Na+].O.O.[CH2:24]([N:35]([CH2:40]C(O)=O)CC(O)=O)[CH2:25][N:26](CC([O-])=O)CC([O-])=O.[Na+].[Na+].[CH2:46](Cl)Cl>C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[NH2:1][CH2:6][CH2:5][CH2:4][C@H:3]1[CH2:46][C@@:2]1([C:24]1[N:35]=[CH:40][N:26]([C:11]2[CH:12]=[CH:13][C:8]([Cl:7])=[CH:9][CH:10]=2)[CH:25]=1)[C:17]([OH:18])=[O:20]

Participants

7

Reactant 5

HCID 1049PyridineHCID 6344DichloromethaneHCID 742994-Chlorophenylboronic acidHCID 516892Sodium BicarbonateHCID 44120005Edta disodium

Product 1

HCID 71183939cis-(1R,2S)-2-(3-aminopropyl)-1-[1-(4-chlorophenyl)imidazol-4-yl]cyclopropane-1-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8895Cupric acetateCatalyst

Procedure

The compound (180 mg) obtained in Reference Example 16 was dissolved in methylene chloride (5 mL). To the solution, copper (II) acetate (76 mg), pyridine (67 μL), molecular sieve 4A (36 mg), and 4-chlorophenylboronic acid (129 mg) were added, and the mixture was stirred overnight at room temperature under an oxygen atmosphere. The progress of the reaction was checked by TLC. Then, a saturated aqueous solution of sodium bicarbonate (10 mL) and disodium ethylenediaminetetraacetate dihydrate (184 mg, 0.49 mmol) were added thereto, and the mixture was stirred for a while. The reaction solution was filtered using a syringe with a filter (Biotage, ISOLUTE Phase Separator) containing an appropriate amount of celite. The filtrate was further washed with methylene chloride. The collected organic layers were combined, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluting solvent: methylene chloride→methylene chloride/ethyl acetate=80/20) to obtain the title compound (190 mg).

Workup

  1. stirringthe mixture was stirred for a while
  2. filtrationThe reaction solution was filtered
  3. filtrationa filter (Biotage, ISOLUTE Phase Separator)
  4. additioncontaining an appropriate amount of celite
  5. washThe filtrate was further washed with methylene chloride
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (eluting solvent: methylene chloride→methylene chloride/ethyl acetate=80/20)

Sources & evidence

ORD record
ord-216eb331eff1430cbfca3a47efca4e27
Source dataset
uspto-grants-2015_02
Patent number
US08946443B2

Reaction notes

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