Citric Acid → ethyl 5-[({6-[(tert-butoxycarbonyl)amino]-2,3-dihydro-1H-inden-5-yl}oxy)methyl]pyrazine-2-carboxylate

HRID 1879396Notes

Reaction equation

HRID 1879396 reaction equation
[OH:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][CH2:8]2)=[CH:4][C:3]=1[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15].Br[CH2:20][C:21]1[N:22]=[CH:23][C:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[N:25][CH:26]=1.C(=O)([O-])[O-].[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[C:14]([O:13][C:12]([NH:11][C:3]1[CH:4]=[C:5]2[C:9]([CH2:8][CH2:7][CH2:6]2)=[CH:10][C:2]=1[O:1][CH2:20][C:21]1[N:22]=[CH:23][C:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[N:25][CH:26]=1)=[O:18])([CH3:15])([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 22050280Ethyl 5-(bromomethyl)pyrazine-2-carboxylateHCID 58398545tert-butyl N-(6-hydroxy-2,3-dihydro-1H-inden-5-yl)carbamate

Product 1

HCID 58398420ethyl 5-[({6-[(tert-butoxycarbonyl)amino]-2,3-dihydro-1H-inden-5-yl}oxy)methyl]pyrazine-2-carboxylateYield 41.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

1.00 g of tert-butyl (6-hydroxy-2,3-dihydro-1H-inden-5-yl)carbamate was dissolved in 10.0 mL of DMF, and 1.08 g of ethyl 5-(bromomethyl)pyrazine-2-carboxylate and 721 mg of potassium carbonate were added thereto, followed by stirring at 60° C. for 1 hour. The reaction liquid was poured into a 5% w/v aqueous citric acid solution, followed by extraction with ethyl acetate. The organic layer was washed with a 5% w/v aqueous citric acid solution, water, and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 7:3) to obtain 690 mg of ethyl 5-[({6-[(tert-butoxycarbonyl)amino]-2,3-dihydro-1H-inden-5-yl}oxy)methyl]pyrazine-2-carboxylate.

Workup

  1. customThe reaction liquid
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with a 5% w/v aqueous citric acid solution, water, and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated
  6. customthe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 7:3)

Sources & evidence

ORD record
ord-919b2524e9874eba8f6d6ccf6d787072
Source dataset
uspto-grants-2012_11
Patent number
US08314240B2

Reaction notes

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