Citric Acid → HCID 71272657, compound

HRID 475103Notes

Reaction equation

HRID 475103 reaction equation
CC1C(C#N)=[CH:4][C:5]2[N:9]=[CH:8][N:7]([CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][O:11]3)C=2C=1.[CH3:19][Mg+].[Br-].[C:22]([OH:34])(=O)[CH2:23][C:24]([CH2:29][C:30](O)=O)([C:26](O)=O)O>C1COCC1>[CH3:26][C:24]1[C:23]([C:22](=[O:34])[CH3:19])=[CH:4][C:5]2[N:9]=[CH:8][N:7]([CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][O:11]3)[C:30]=2[CH:29]=1

Participants

5

Reactant 3

HCID 311Citric AcidHCID 71272633HCID 71272633, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 71272657HCID 71272657, compoundYield 90.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole-5-carbonitrile (1.1 g, 4.6 mmol) in anhydrous THF (20 mL) under nitrogen at 0° C. was dropped a solution of CH3MgBr in THF (8 mL, 24 mmol) at a rate that the internal reaction temperature remained below 10° C. After the addition, the reaction mixture was stirred at RT overnight. The mixture was slowly poured into ice-water (20 mL) and stirred at RT for 0.5 h. The solution's pH was adjusted to 5.0˜6.0 by using citric acid, and mixture was extracted with EtOAc (20 mL×3). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with petroleum ether/EtOAc (1:1) to afford 1-(6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)ethanone as a yellow solid (1.1 g, 90.1%). MS (ESI): m/z=259.2 [M+1]+.

Workup

  1. customremained below 10° C
  2. additionAfter the addition
  3. stirringstirred at RT for 0.5 h
  4. extractionwas extracted with EtOAc (20 mL×3)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by SiO2 chromatography
  9. washeluting with petroleum ether/EtOAc (1:1)

Sources & evidence

ORD record
ord-a5935ad5bc9348fbaf0441fec678c345
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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