Water → HCID 59529925, compound

HRID 1894953Notes

Reaction equation

HRID 1894953 reaction equation
C([O:3][C:4](=O)[CH2:5][CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([C:14]2[NH:15][C:16]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:13])[CH2:7]1)C.[BH4-].[Li+].O>C1COCC1>[NH:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:22]=[C:14]1[C:12]([N:8]1[CH2:9][CH2:10][CH2:11][CH:6]([CH2:5][CH2:4][OH:3])[CH2:7]1)=[O:13]

Participants

5

Reactant 3

HCID 962WaterHCID 4148881Lithium borohydrideHCID 131730822HCID 131730822, compound

Product 1

HCID 59529925HCID 59529925, compoundYield 27.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 500 mg of indole-2-carboxylic acid and 530 mg of ethyl piperidin-3-yl acetate in 8 mL of DMF were added 610 mg of 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride and 430 mg of 1-hydroxybenzotriazole, followed by stirring at room temperature for 2 hours. 0.5M aqueous hydrochloric acid was added to the reaction liquid, followed by extraction with ethyl acetate. The organic layer was washed with 0.5M aqueous sodium hydroxide solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain 519 mg of ethyl[1-(1H-indol-2-ylcarbonyl)piperidin-3-yl]acetate. To a solution of 392 mg of the resulting ethyl[1-(1H-indol-2-ylcarbonyl)piperidin-3-yl]acetate in 7 mL of THF was added 30 mg of lithium borohydride, followed by stirring at room temperature for 1 day. Water was added to the reaction liquid, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography [hexane:ethyl acetate=1:0-2:1], and then crystallized from diisopropyl ether to obtain 92 mg of 2-[1-(1H-indol-2-ylcarbonyl)piperidin-3-yl]ethanol as a white solid.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography [hexane:ethyl acetate=1:0-2:1]
  6. customcrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-492399f40e464859a5482c0a31cec8b5
Source dataset
uspto-grants-2013_08
Patent number
US08513422B2

Reaction notes

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