Sulfuric acid magnesium salt (1:1) → 6-[(3-Ethoxycarbonyl-propylamino)-methyl]-indole-1-carboxylic acid tert-butyl ester

HRID 408589Notes

Reaction equation

HRID 408589 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:10])[CH2:6][CH2:7][CH2:8][NH2:9])[CH3:3].[C:11]([O:15][C:16]([N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([CH:27]=O)[CH:25]=2)[CH:20]=[CH:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].[O-]S([O-])(=O)=O.[Mg+2].[BH4-].[Na+]>CCO.CO>[C:11]([O:15][C:16]([N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([CH2:27][NH:9][CH2:8][CH2:7][CH2:6][C:5]([O:4][CH2:2][CH3:3])=[O:10])[CH:25]=2)[CH:20]=[CH:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 4311764Sodium borohydrideHCID 126496614-Aminobutyrate ethyl hydrochlorideHCID 14616867Tert-butyl 6-formyl-1H-indole-1-carboxylate

Product 1

HCID 705578626-[(3-Ethoxycarbonyl-propylamino)-methyl]-indole-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 4-amino-butyric acid ethyl ester hydrochloride (1 eq.) in either MeOH or EtOH were added TEA (2.5 eq.), 6-formyl-indole-1-carboxylic acid tert-butyl ester (0.95 eq.) and MgSO4 (1.5 eq.). The reaction was stirred at 20° C. for 15 h, then cooled to −15° C. NaBH4 (2 to 6 eq.) was added portionwise. The reaction was stirred for 1 h at −15° C., then 1 h at 0° C. The reaction was quenched with the addition of cold water at 0° C. The crude was extracted three times with DCM. The organic layers were combined, dried over MgSO4, filtered and concentrated under reduced pressure at 20° C. The crude was purified by chromatography on silica gel (elution with DCM/MeOH: 1/0 to 99/1) to afford 6-[(3-ethoxycarbonyl-propylamino)-methyl]-indole-1-carboxylic acid tert-butyl ester.

Workup

  1. temperaturecooled to −15° C
  2. stirringThe reaction was stirred for 1 h at −15° C.
  3. custom1 h
  4. customat 0° C
  5. customThe reaction was quenched with the addition of cold water at 0° C
  6. extractionThe crude was extracted three times with DCM
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure at 20° C
  10. customThe crude was purified by chromatography on silica gel (elution with DCM/MeOH: 1/0 to 99/1)

Sources & evidence

ORD record
ord-8e6cc5d960eb4dc8a9f042f556ac79f3
Source dataset
uspto-grants-2014_06
Patent number
US08759334B2

Reaction notes

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