Ethyl Acetate → (R)-3-(N-benzyloxycarbonylpyrrolidin-2-ylcarbonyl)-5-dibenzylamino-1H-indole

HRID 1683925Notes

Reaction equation

HRID 1683925 reaction equation
[CH2:1]([N:8]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:25]([Mg]Br)[CH3:26].[C:29]([O:32][CH2:33][CH3:34])(=[O:31])C.[C:35](=[O:38])([O-])O.[Na+]>CCOCC>[CH2:33]([O:32][C:29]([N:8]1[CH2:26][CH2:25][CH2:2][C@@H:1]1[C:35]([C:12]1[C:11]2[C:15](=[CH:16][CH:17]=[C:9]([N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:10]=2)[NH:14][CH:13]=1)=[O:38])=[O:31])[C:34]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 9972827N,N-dibenzyl-1H-indol-5-amineHCID 178418443HCID 178418443, compound

Product 1

HCID 10414998(R)-3-(N-benzyloxycarbonylpyrrolidin-2-ylcarbonyl)-5-dibenzylamino-1H-indole

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Procedure

To a stirred mixture of (R)-N-carbobenzyloxyproline (3.59 g, 14.41 mmol) and N,N-dimethylformamide (0.1 mL) in methylene chloride (45 mL) was added dropwise oxalyl chloride (1.87 mL, 21.62 mmol, 1.5 eq). The resulting effervescing mixture was stirred at room temperature under nitrogen for 1.5 hours. The reaction solution was then evaporated under reduced pressure, yielding the residue [(R)-N-carbobenzyloxyproline acid chloride] which was dissolved in anhydrous ether (50 mL). This solution was added dropwise to a stirred, preformed solution of 5-dibenzylaminoindole (9.00 g, 28.81 mmol, 2.0 eq) and ethyl magnesium bromide (3.0M in ether, 10.08 mL, 30.25 mmol, 2.1 eq) in anhydrous ether (75 mL), which had been stirring at room temperature under nitrogen for 30 minutes prior to the addition of the ethereal solution of the (R)-N-carbobenzyloxyproline acid chloride. The resulting reaction mixture was stirred at room temperature under nitrogen for 30 minutes, and then ethyl acetate (100 mL) and a saturated solution of sodium hydrogen carbonate (75 mL) were added. The organic layer was removed, and the aqueous layer was extracted with ethyl acetate (100 mL). The organic extracts were combined, dried (MgSO4), and evaporated under reduced pressure to afford a green oil. Trituration of this oil in anhydrous ether (50 mL) afforded the title compound as a white solid: mp, 176.0°-177.0° C.; LRMS (m/z, relative intensity) 543 (100, M+), 453 (10), 407 (7), 339 (40), 307 (10), 247 (10), 154 (38); [α]25 =+112° (THF, c=1.0); Anal. calcd. for C35H33N3O3 : C, 77.32; H, 6.12; N, 7.73. Found: C, 77.35; H, 6.30; N, 7.66.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature under nitrogen for 30 minutes
  3. customThe organic layer was removed
  4. extractionthe aqueous layer was extracted with ethyl acetate (100 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated under reduced pressure
  7. customto afford a green oil

Sources & evidence

ORD record
ord-d7f3342c0fab4e70a9f692ae82f5c550
Source dataset
uspto-grants-1997_06
Patent number
US05639752

Reaction notes

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