Diisopropylamine → Ethyl 6,7,8,9-tetrahydro-6-oxopyrido[1,2-a]indole-7-carboxylate

HRID 863674Notes

Reaction equation

HRID 863674 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH:13]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:14]=1[CH:15]=[C:16]1[CH2:25][CH2:24][CH2:23][C:22](=[O:26])[N:17]12.Cl[C:28]([O:30][CH2:31][CH3:32])=[O:29]>CCCCCC.O1CCCC1>[O:26]=[C:22]1[N:17]2[C:18]3[C:14]([CH:15]=[C:16]2[CH2:25][CH2:24][CH:23]1[C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:13][CH:21]=[CH:20][CH:19]=3

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 10928Ethyl chloroformateHCID 110845538,9-dihydropyrido[1,2-a]indol-6(7H)-oneHCID 178418339Butyllithium

Product 1

HCID 19696382Ethyl 6,7,8,9-tetrahydro-6-oxopyrido[1,2-a]indole-7-carboxylateYield 52.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-20 °C

Procedure

6.6 ml of a 1.6M solution of n-butyllithium in n-hexane were added to a stirred solution of 1.11 g of diisopropylamine in 150 ml of tetrahydrofuran at -78° C. under nitrogen. The mixture was allowed to warm to -20° C. for 5 minutes and was then again cooled to -78° C. Then, 1.85 g of 6,7,8,9-tetrahydropyrido[1,2-a]indol-6-one in 10 ml of tetrahydrofuran were added dropwise. After stirring at -78° C. for 0.5 hour, 1.19 g of ethyl chloroformate were added and the mixture was allowed to warm to room temperature. The solvent was removed by evaporation and the residue was partitioned between diethyl ether and 2M hydrochloric acid. The ethereal extracts were washed with saturated sodium bicarbonate solution, dried and concentrated to give an oil. This oil was purified by chromatography on silica gel with dichloromethane. Crystallization of the product from methanol gave 1.35 g of ethyl 6,7,8,9-tetrahydro-6-oxopyrido[1,2-a]indole-7-carboxylate of melting point 82°-84° C.

Workup

  1. temperaturewas then again cooled to -78° C
  2. temperatureto warm to room temperature
  3. customThe solvent was removed by evaporation
  4. customthe residue was partitioned between diethyl ether and 2M hydrochloric acid
  5. washThe ethereal extracts were washed with saturated sodium bicarbonate solution
  6. customdried
  7. concentrationconcentrated
  8. customto give an oil
  9. customThis oil was purified by chromatography on silica gel with dichloromethane
  10. customCrystallization of the product from methanol

Sources & evidence

ORD record
ord-f978dd1c738b493988574082519d8bb9
Source dataset
uspto-grants-1998_02
Patent number
US05721245

Reaction notes

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