Sodium borohydride → ethyl 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxylate

HRID 1748265Notes

Reaction equation

HRID 1748265 reaction equation
[C:1]([CH2:3][CH2:4][N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:12]=2)[CH:7]=[C:6]1[C:19]([O:21]CC)=O)#[N:2].[BH4-].[Na+]>C1COCC1.CO.CCOC(C)=O>[O:21]=[C:19]1[C:6]2=[CH:7][C:8]3[CH:9]=[CH:10][C:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:12][C:13]=3[N:5]2[CH2:4][CH2:3][CH2:1][NH:2]1

Participants

6

Reactant 2

HCID 4311764Sodium borohydride2×HCID 67235491diethyl 1-(2-cyanoethyl)-1H-indole-2,6-dicarboxylate

Product 1

HCID 67235463ethyl 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxylateYield 85%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of diethyl 1-(2-cyanoethyl)-1H-indole-2,6-dicarboxylate (1.5 g, 4.8 mmol) in THF (12 mL) and methanol (16 mL) is added CoCl2 (1.3 g, 9.6 mmol). The bright blue suspension/solution is cooled to 0° C., and NaBH4 (1.8 g, 48.0 mmol) is carefully added in small portions. As each portion is added H2 is formed violently and the suspension becomes black. After the addition of NaBH4 is complete, the mixture is warmed up room temperature for 60 min and is then heated at reflux for 16 h. The mixture is cooled to room temperature and is diluted with EtOAc. The mixture is filtered through Celite, and the gummy solids are washed with EtOAc. The combined EtOAc filtrate is washed with 3M HCl, water, NaHCO3, brine, dried (Na2SO4) and concentrated to afford the title crude compound (1.1 g, 85%) which is used in the next step without purification.

Workup

  1. additionAs each portion is added H2
  2. customis formed violently
  3. temperaturethe mixture is warmed up room temperature for 60 min
  4. temperatureis then heated
  5. temperatureat reflux for 16 h
  6. temperatureThe mixture is cooled to room temperature
  7. filtrationThe mixture is filtered through Celite
  8. washthe gummy solids are washed with EtOAc
  9. washThe combined EtOAc filtrate is washed with 3M HCl, water, NaHCO3, brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-4fe57b1766ca47019f3a347e9f0c3805
Source dataset
uspto-grants-2015_10
Patent number
US09150577B2

Reaction notes

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