Ethyl chloroformate → N-(1H-indol-1-yl) carbamic acid ethyl ester

HRID 703460Notes

Reaction equation

HRID 703460 reaction equation
C([O-])(O)=O.[Na+].[N:6]1([NH2:15])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7]1.Cl[C:17]([O:19][CH2:20][CH3:21])=[O:18]>ClCCl>[CH2:20]([O:19][C:17](=[O:18])[NH:15][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)[CH3:21]

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 516892Sodium BicarbonateHCID 6432211-Aminoindole

Product 1

HCID 10512386N-(1H-indol-1-yl) carbamic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of NaHCO3 (50 g) in 100 ml dichloromethane (DCM) was added a solution of 1H-indol-1-amine (36 g) in 200 ml DCM. After cooling to 0° C. with an ice bath, a solution of ethyl chloroformate (29 ml) in 50 ml DCM was added over a period of thirty minutes. After stirring at ambient temperature for three hours, the mixture was filtered, and the filtrate washed with water, then dried (saturated NaCl, anhydrous MgSO4). After filtering, the solvent was evaporated to an oil which was eluted on a silica gel column with DCM, via HPLC to give N-(1H-indol-1-yl) carbamic acid ethyl ester, 33.6 g (61%) as an oil. To a cold solution of N-(1H-indol-1-yl) carbamic acid ethyl ester (15 g) in 100 ml tetrahydrofuran, was added potassium t-butoxide (9 g) and the mixture stirred at 5° C. for one hour. To this was added 1-bromopropane (7.3 ml) and the mixture stirred at ambient temperature for five hours. The mixture was poured into 300 ml iced-water, stirred for five minutes, then extracted with ethyl acetate. The organic layer was washed with water, then dried (saturated, NaCl, anhydrous MgSO4). After filtering, the solvent was evaporated to give N-(1H-indol-1-yl)-N-propylcarbamic acid ethyl ester as an oil, 16.5 g (91%). To a solution of N-(1H-indol-1-yl)-N-propylcarbamic acid ethyl ester (16.5 g) in 35 ml ethylene glycol, was added a solution of NaOH (10 g) in 30 ml water. After stirring at 120° C. for four hours, the mixture was poured into 300 ml ice water, stirred for five minutes, then extracted with ethyl acetate. The organic layer was washed with water, then dried (saturated NaCl, anhydrous MgSO4). After filtering, the solvent was evaporated to give N-(1H-indol-1-yl)-N-propylamine, 9.0 g (78%) as an oil.

Workup

  1. filtrationthe mixture was filtered
  2. washthe filtrate washed with water
  3. dry with materialdried (saturated NaCl, anhydrous MgSO4)
  4. filtrationAfter filtering
  5. customthe solvent was evaporated to an oil which
  6. washwas eluted on a silica gel column with DCM, via HPLC

Sources & evidence

ORD record
ord-74fd694b95254aa0b9b7c6cf1eb1930e
Source dataset
uspto-grants-1991_01
Patent number
US04983608

Reaction notes

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