Acetic Acid Mixture with Hydrobromic Acid → 1H-Indole, 5-bromo-3-(2-pyrrolidinylmethyl)-, (R)-

HRID 1441077Notes

Reaction equation

HRID 1441077 reaction equation
C(OC([N:11]1[CH2:15][CH2:14][CH2:13][C@@H:12]1[CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([Br:26])[CH:24]=2)[NH:19][CH:18]=1)=O)C1C=CC=CC=1.Br.C(O)(=O)C>>[NH3:11].[Br:26][C:23]1[CH:24]=[C:25]2[C:20](=[CH:21][CH:22]=1)[NH:19][CH:18]=[C:17]2[CH2:16][C@H:12]1[CH2:13][CH2:14][CH2:15][NH:11]1

Participants

4

Reactant 2

HCID 21893785Acetic Acid Mixture with Hydrobromic AcidHCID 22859561(R)-Benzyl 2-((5-bromo-1H-indol-3-yl)methyl)pyrrolidine-1-carboxylate

Product 2

HCID 222AmmoniaHCID 228595901H-Indole, 5-bromo-3-(2-pyrrolidinylmethyl)-, (R)-Yield 59.5%

Procedure

To 3-(1-benzyloxycarbonylpyrrolidin-2(R)-ylmethyl)-5-bromo-1H-indole (see Preparation 35B) (10.0 g, 24.2 mmol) was added dropwise hydrogen bromide/acetic acid (36% w/w) (17 ml) at 0° C., with stirring. After 50 minutes at 0° C. the solvent was removed by evaporation under reduced pressure, and the residue azeotroped with toluene. The resulting oil was partitioned between dichloromethane and 2M aqueous sodium carbonate. The separated aqueous phase was re-extracted with dichloromethane and the combined organic phases dried (Na2SO4) and evaporated under reduced pressure. Purification by column chromatography on silica gel, eluting with a gradient of dichloromethane: methanol:0.88 aqueous ammonia (95:5:0 to 95:5:2), yielded the title compound as an oil (2.01 g). Found: C,54.75; H,5.41; N,9.63. C13H15BrN2.1/5CH2Cl2 requires: C,54.84; H,5.37; N,9.67%.

Workup

  1. customAfter 50 minutes at 0° C. the solvent was removed by evaporation under reduced pressure
  2. customthe residue azeotroped with toluene
  3. customThe resulting oil was partitioned between dichloromethane and 2M aqueous sodium carbonate
  4. extractionThe separated aqueous phase was re-extracted with dichloromethane
  5. dry with materialthe combined organic phases dried (Na2SO4)
  6. customevaporated under reduced pressure
  7. customPurification by column chromatography on silica gel
  8. washeluting with a gradient of dichloromethane

Sources & evidence

ORD record
ord-d28f73dafdd64bfabea755c393d07a0e
Source dataset
uspto-grants-1996_03
Patent number
US05502065

Reaction notes

Loading…