Hydrochloric Acid → (3-Benzyl-pyrrolidin-3-yl)-(1H-indol-5-yl)-methanone

HRID 1894997Notes

Reaction equation

HRID 1894997 reaction equation
Cl.C(OC([N:9]1[CH2:13][CH2:12][C:11]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:14]([C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[NH:21][CH:20]=[CH:19]3)=[O:15])[CH2:10]1)=O)(C)(C)C>CO>[CH2:25]([C:11]1([C:14]([C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[NH:21][CH:20]=[CH:19]3)=[O:15])[CH2:12][CH2:13][NH:9][CH2:10]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 666872373-benzyl-3-(1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 25024305(3-Benzyl-pyrrolidin-3-yl)-(1H-indol-5-yl)-methanoneYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of HCl (1.0 M in MeOH, 12 mL) was added to a solution of 3-benzyl-3-(1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester enantiomer A (257 mg, 0.635 mmol) in MeOH (5 mL). The resulting pale yellow solution was stirred at room temperature for 6 hours, then cooled to 0° C. and quenched by addition of aqueous NaOH (1.0 M). The mixture was diluted with water and extracted with DCM. The combined organic layers were dried over MgSO4, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography (5% to 10% of MeOH in DCM with 0.5% of NH4OH) to give 179 mg (93% yield) of (3-Benzyl-pyrrolidin-3-yl)-(1H-indol-5-yl)-methanone, which was dissolved in a mixture of DCM/MeOH. A solution of HCl (1 M in Et2O) was added, and the resulting mixture was evaporated under reduced pressure and the residue was triturated with Et2O to give 173 mg of (3-benzyl-pyrrolidin-3-yl)-(1H-indol-5-yl)-methanone hydrochloride enantiomer A as a white powder. MS=305 [M+H]+; [α]D=−26.3° (5.40 mg/1.0 mL of MeOH).

Workup

  1. temperaturecooled to 0° C.
  2. customquenched by addition of aqueous NaOH (1.0 M)
  3. additionThe mixture was diluted with water
  4. extractionextracted with DCM
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe residue was purified by flash chromatography (5% to 10% of MeOH in DCM with 0.5% of NH4OH)

Sources & evidence

ORD record
ord-c1678ce82d3f4cd08bfdcce6619d7591
Source dataset
uspto-grants-2013_08
Patent number
US08513425B2

Reaction notes

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