Ammonium Hydroxide → 2-t-Butoxycarbonyl-9-carbamoyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole

HRID 2301081Notes

Reaction equation

HRID 2301081 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:20][CH2:19][C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCCCCC.C([Li])CCC.ClC(Cl)(O[C:36](=[O:42])OC(Cl)(Cl)Cl)Cl.[NH4+:44].[OH-]>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:20][CH2:19][C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([C:36](=[O:42])[NH2:44])[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 14923Ammonium HydroxideHCID 94429TriphosgeneHCID 18377349tert-butyl 3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylateHCID 178418244HCID 178418244, compound

Product 1

HCID 183772812-t-Butoxycarbonyl-9-carbamoyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoleYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A 10 ml portion of tetrahydrofuran (THF) solution containing 600 mg (2.20 mmol) of 2-t-butoxycarbonyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole was cooled to −78° C., mixed with 4.13 ml (6.60 mmol) of 1.6 M n-butyl lithium hexane solution and stirred for 30 minutes, while temperature of the reaction solution increased to −45° C. This was mixed with 6 ml of THF solution containing 1.31 g (4.40 mmol) of triphosgene and stirred for 3.5 hours, while temperature of the reaction solution increased to 0° C. After additional 2 hours of stirring at room temperature, the reaction solution was again cooled to −30° C. This was mixed with 20 ml of 28% ammonia aqueous solution, stirred for 30 minutes and then extracted with chloroform. The extract was washed with water, hydrochloric acid in that order and dried (Na2SO4), and then the solvent was removed by evaporation under a reduced pressure and the resulting oily material was purified by a silica gel column chromatography (140 cc; elution by ethyl acetate-hexane=2:5) to obtain 469 mg of the title compound (68% in yield).

Workup

  1. temperatureincreased to −45° C
  2. stirringstirred for 3.5 hours, while temperature of the reaction solution
  3. temperatureincreased to 0° C
  4. stirringAfter additional 2 hours of stirring at room temperature
  5. temperaturethe reaction solution was again cooled to −30° C
  6. stirringstirred for 30 minutes
  7. extractionextracted with chloroform
  8. washThe extract was washed with water, hydrochloric acid in that order
  9. dry with materialdried (Na2SO4)
  10. customthe solvent was removed by evaporation under a reduced pressure
  11. customthe resulting oily material was purified by a silica gel column chromatography (140 cc; elution by ethyl acetate-hexane=2:5)

Sources & evidence

ORD record
ord-def78da142424080a629097f1bb48943
Source dataset
uspto-grants-2002_12
Patent number
US06498251B1

Reaction notes

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