Sodium hydride → 5-methanesulphonyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1677047Notes

Reaction equation

HRID 1677047 reaction equation
C([N:8]1[CH2:20][CH2:19][C:11]2[NH:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=3[C:10]=2[CH2:9]1)(OC(C)(C)C)=O.[H-].[Na+].[CH3:23][S:24](Cl)(=[O:26])=[O:25]>CN(C=O)C>[CH3:23][S:24]([N:12]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=2[C:10]2[CH2:9][NH:8][CH2:20][CH2:19][C:11]1=2)(=[O:26])=[O:25]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 46344376tert-Butyl 1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate

Product 1

HCID 575412745-methanesulphonyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleYield 18.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-Boc-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (800 mg, 2.94 mmol) was dissolved in DMF (20 mL) and stirred at room temperature. The vessel was flushed with argon and sodium hydride (235 mg, 5.87 mmol) was added. After 30 minutes, the reaction was cooled to 0° C. and methanesulphonyl chloride (0.46 mL, 5.87 mmol) was added dropwise over 5 minutes. The mixture was stirred and allowed to warm to room temperature overnight and the solvent removed in vacuo. TLC and LCMS showed that the BOC group was removed during this process. Therefore the residue was partitioned between 2M aqueous sodium hydroxide (30 mL) and dichloromethane (2×100 mL) and combined organics treated with brine (30 mL), dried (sodium sulphate), concentrated in vacuo. Flash column chromatography (silica, eluting with 100% dichloromethane/5% methanolic ammonia in 50% ethanol/dichloromethane) gave 5-methanesulphonyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole as a pale yellow brittle solid (135 mg, 18%).

Workup

  1. additionwas added
  2. temperaturethe reaction was cooled to 0° C.
  3. stirringThe mixture was stirred
  4. temperatureto warm to room temperature overnight
  5. customthe solvent removed in vacuo
  6. customwas removed during this process
  7. customTherefore the residue was partitioned between 2M aqueous sodium hydroxide (30 mL) and dichloromethane (2×100 mL)
  8. additioncombined organics treated with brine (30 mL)
  9. dry with materialdried (sodium sulphate)
  10. concentrationconcentrated in vacuo
  11. washFlash column chromatography (silica, eluting with 100% dichloromethane/5% methanolic ammonia in 50% ethanol/dichloromethane)

Sources & evidence

ORD record
ord-1d7dd8d8408b442a97d0fb39be4cbe2a
Source dataset
uspto-grants-2011_08
Patent number
US08008279B2

Reaction notes

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