Hydrochloric Acid → ethyl 2-amino-3-(4-bromo-7-carbamoyl-1H-indol-3-yl)propanoate

HRID 2361435Notes

Reaction equation

HRID 2361435 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:8]([C:11](=[O:13])[NH2:12])=[C:7]2[C:3]=1[C:4]([CH2:14][CH:15]([N+:21]([O-])=O)[C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:5][NH:6]2.Cl.[OH-].[Na+]>C(O)(C)C.C1COCC1.CCOC(C)=O.[Zn]>[NH2:21][CH:15]([CH2:14][C:4]1[C:3]2[C:7](=[C:8]([C:11](=[O:13])[NH2:12])[CH:9]=[CH:10][C:2]=2[Br:1])[NH:6][CH:5]=1)[C:16]([O:18][CH2:19][CH3:20])=[O:17]

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 86681529Ethyl 3-(4-bromo-7-carbamoyl-1H-indol-3-yl)-2-nitropropanoate

Product 1

HCID 67994549ethyl 2-amino-3-(4-bromo-7-carbamoyl-1H-indol-3-yl)propanoateYield 86.1%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of ethyl 3-(4-bromo-7-carbamoyl-1H-indol-3-yl)-2-nitropropanoate (4.6 g, 11.97 mmol) in isopropanol (200 mL) and THF (100 mL) was cooled in an ice bath and treated portionwise with zinc dust (8.85 g, 135 mmol), followed by 1 M aqueous HCl (150 mL) in portions. The mixture was stirred at room temperature for 3 h, then treated with NaOH pellets and 1 M aqueous NaOH to pH 9-10. The mixture was diluted with THF and EtOAc, stirred for 15 min and filtered through a CELITE® pad. The solids were rinsed with EtOAc, THF, and NaHCO3 (aq). The filtrates were concentrated to remove most of the organic solvents, and the aqueous residue was extracted with EtOAc. The combined extracts were washed with brine, dried and concentrated to provide the desired product as an off-white solid (3.65 g, 86% yield). LCMS (M+H)+ m/z 353.8, 355.8.

Workup

  1. stirringstirred for 15 min
  2. filtrationfiltered through a CELITE® pad
  3. washThe solids were rinsed with EtOAc, THF, and NaHCO3 (aq)
  4. concentrationThe filtrates were concentrated
  5. customto remove most of the organic solvents
  6. extractionthe aqueous residue was extracted with EtOAc
  7. washThe combined extracts were washed with brine
  8. customdried
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-df0472a9bbc444f99ef5f65d47bf88fd
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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