Sodium hydride → tert-butyl 5-methoxycarbonylmethyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate

HRID 1677028Notes

Reaction equation

HRID 1677028 reaction equation
[C:1]([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)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].Br[CH2:24][C:25]([O:27][CH3:28])=[O:26]>CN(C=O)C>[CH3:28][O:27][C:25]([CH2:24][N:12]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=2[C:10]2[CH2:9][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:20][CH2:19][C:11]1=2)=[O:26]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 46344376tert-Butyl 1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate

Product 1

HCID 57681625tert-butyl 5-methoxycarbonylmethyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

N-boc-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (450 mg, 1.65 mmol) was dissolved in DMF (7 mL) and stirred at room temperature. The vessel was flushed with argon and sodium hydride (67.0 mg, 1.65 mmol) was added. After 30 minutes, methyl bromoacetate (253 mg, 1.65 mmol) in DMF (2 mL) was added and the mixture stirred overnight. The solvent was removed in vacuo and the residue partitioned between brine (20 mL) and ethyl acetate (2×40 mL). Combined organics were dried (sodium sulphate), concentrated in vacuo and adsorbed onto silica for purification by flash chromatography (0-40% ethyl acetate/isohexane). This gave tert-butyl 5-methoxycarbonylmethyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate as a pale yellow foam (387 mg, 68%).

Workup

  1. additionwas added
  2. stirringthe mixture stirred overnight
  3. customThe solvent was removed in vacuo
  4. customthe residue partitioned between brine (20 mL) and ethyl acetate (2×40 mL)
  5. dry with materialCombined organics were dried (sodium sulphate)
  6. concentrationconcentrated in vacuo
  7. customadsorbed onto silica for purification by flash chromatography (0-40% ethyl acetate/isohexane)

Sources & evidence

ORD record
ord-43f7852d089b48d6af25f42da8975aec
Source dataset
uspto-grants-2011_08
Patent number
US08008279B2

Reaction notes

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