N-Methyl dicyclohexylamine → 2-tert-butyl-3-(2,2-dimethoxy-ethyl)-6-nitro-1H-indole

HRID 549382Notes

Reaction equation

HRID 549382 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[NH2:11].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[CH3:46][O:47][CH:48]([O:56][CH3:57])[CH2:49][C:50]#[C:51][C:52]([CH3:55])([CH3:54])[CH3:53].C1(N(C2CCCCC2)C)CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN(C)C=O>[C:52]([C:51]1[NH:11][C:3]2[C:2]([C:50]=1[CH2:49][CH:48]([O:56][CH3:57])[O:47][CH3:46])=[CH:7][CH:6]=[C:5]([N+:8]([O-:10])=[O:9])[CH:4]=2)([CH3:55])([CH3:53])[CH3:54]

Participants

7

Reactant 4

HCID 24210N-Methyl dicyclohexylamineHCID 826072-Bromo-5-nitroanilineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 578992311,1-Dimethoxy-5,5-dimethyl-hex-3-yne

Product 1

HCID 578992342-tert-butyl-3-(2,2-dimethoxy-ethyl)-6-nitro-1H-indoleYield 20%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

2-Bromo-5-nitro-phenylamine (4.9 g, 22.6 mol), Pd2(dba)3 (207 mg, 0.226 mmol), and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (431 mg, 0.904 mmol) was added in a dry 500 mL round-bottom flask. The flask was evacuated and purged with nitrogen three times. 1,1-Dimethoxy-5,5-dimethyl-hex-3-yne (4.61 g, 27.1 mmol), dicyclohexyl-methyl-amine (14.5 mL, 67.8 mmol) and N,N-dimethylformamide (56.5 mL) was added. The reaction mixture was stirred at 100° C. for 24 h, cooled to room temperature, and filtered through a pad of Celite, which was rinsed with ethyl acetate. The filtrate and wash were combined, washed with water and a saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography to give the title compound as an orange powder (1.41 g, 20%). LCMS (m/z): 307.1 (M+1).

Workup

  1. customThe flask was evacuated
  2. custompurged with nitrogen three times
  3. temperaturecooled to room temperature
  4. filtrationfiltered through a pad of Celite, which
  5. washwas rinsed with ethyl acetate
  6. washThe filtrate and wash
  7. washwashed with water
  8. dry with materiala saturated sodium chloride solution, dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-09cc150b5bab44bfa2d77b8ba4622b70
Source dataset
uspto-grants-2011_05
Patent number
US07943652B2

Reaction notes

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