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

HRID 975161Notes

Reaction equation

HRID 975161 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+].Cl>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

5

Reactant 3

HCID 313Hydrochloric AcidHCID 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

3-(N-Benzyloxycarbonyl-2(R)-pyrrolidinylcarbonyl)-5-bromo-1H-indole (WO-A-92/06973; 0.67 g, 1.57 mmol) was dissolved in dry tetrahydrofuran (20 ml) and, at room temperature under nitrogen, lithium borohydride (2M solution in tetrahydrofuran; 1.2 ml, 2.4 mmol) was added. The reaction mixture was stirred at room temperature for 3 hours, heated under reflux for 16 hours, then allowed to cool to room temperature. 2M Hydrochloric acid (10 ml) was added dropwise and the reaction mixture then partitioned between ethyl acetate and water. The separated organic phase was washed with saturated aqueous sodium bicarbonate solution (×2) and brine (×1), dried (Na2SO4), and evaporated under reduced pressure 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). Rf 0.20 (SS 16). Found: C,59.94; H,5.07; N,6.58. C21H21BrN2O2 ; 0.10 CH2Cl2 requires C,60.08; H,5.07; N,6.64%. δ(CDCl3)--mixture of rotamers: 1.63-1.90 (4H, m), 2.60-2.82 (1H, m), 3.10-3.28 (1H, m), 3.30-3.54 (2H, m), 4.18 (1H, m), 5.15-5.25 (2H, m), 5.30 (0.2H, s, CH2Cl2), 6.90 and 6.95 (1H, 2×s), 7.05-7.50 (7H, m), 7.70 and 7.85 (1H, 2×s), 8.25 (1H, br s).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 16 hours
  3. temperatureto cool to room temperature
  4. customthe reaction mixture then partitioned between ethyl acetate and water
  5. washThe separated organic phase was washed with saturated aqueous sodium bicarbonate solution (×2) and brine (×1)
  6. dry with materialdried (Na2SO4)
  7. customevaporated under reduced pressure
  8. customto give a colourless oil
  9. customPurification by column chromatography on silica gel
  10. washeluting with dichloromethane

Sources & evidence

ORD record
ord-ecb5fc58d8f147e48232c6550ac9818b
Source dataset
uspto-grants-1997_03
Patent number
US05607960

Reaction notes

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