Lithium borohydride → (R)-Benzyl 2-((5-bromo-1H-indol-3-yl)methyl)pyrrolidine-1-carboxylate

HRID 744147Notes

Reaction equation

HRID 744147 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@@H:12]1[C:16]([C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([Br:27])[CH:25]=2)[NH:20][CH:19]=1)=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Li+]>O1CCCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@@H:12]1[CH2:16][C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([Br:27])[CH:25]=2)[NH:20][CH:19]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 11224090Phenylmethyl (2R)-2-((5-bromo-1H-indol-3-yl)carbonyl)-1-pyrrolidinecarboxylate

Product 1

HCID 22859561(R)-Benzyl 2-((5-bromo-1H-indol-3-yl)methyl)pyrrolidine-1-carboxylateYield 49.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(R)-3-(N-Benzyloxycarbonylpyrrolidin-2-yl-carbonyl)-5-bromo-1H-indole(0.67 g, 1.57 mmol) was dissolved in anhydrous tetrahydrofuran (20 mL) and at room temperature under nitrogen was added lithium borohydride (2 molar in tetrahydrofuran) (1.2 mL, 2.4 mmol). The reaction mixture was stirred at room temperature for 3 hours and warmed to reflux for 16 hours. After cooling to room temperature, 2NHCl (10 mL) was added dropwise and the reaction mixture partitioned between ethyl acetate and water. The separated organic phase was washed with saturated aqueous sodium hydrogen carbonate (2×), brine (1×), dried (Na2SO4), and evaporated in vacuo to give a colourless oil. Purification by column chromatography on silica gel, eluting with dichloromethane gave the title compound as an oil (0.32 g). TLC (SiO2 :CH2Cl2): Rf =0.2.

Workup

  1. temperaturewarmed
  2. temperatureto reflux for 16 hours
  3. temperatureAfter cooling to room temperature
  4. addition2NHCl (10 mL) was added dropwise
  5. customthe reaction mixture partitioned between ethyl acetate and water
  6. washThe separated organic phase was washed with saturated aqueous sodium hydrogen carbonate (2×), brine (1×)
  7. dry with materialdried (Na2SO4)
  8. customevaporated in vacuo
  9. customto give a colourless oil
  10. customPurification by column chromatography on silica gel
  11. washeluting with dichloromethane

Sources & evidence

ORD record
ord-f2caec0871104f98bae9aefe845a8c9d
Source dataset
uspto-grants-1996_09
Patent number
US05559129

Reaction notes

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