Ethyl Acetate → methyl 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylate

HRID 2068878Notes

Reaction equation

HRID 2068878 reaction equation
[CH3:1][C:2]1([CH3:24])[CH2:10][C:9]2[NH:8][N:7]=[C:6]([C:11]3[NH:12][C:13]4[C:18]([CH:19]=3)=[CH:17][CH:16]=[C:15]([C:20]([O:22][CH3:23])=[O:21])[CH:14]=4)[C:5]=2[CH2:4][CH2:3]1.[H-].[Na+].[CH3:27][Si:28]([CH3:35])([CH3:34])[CH2:29][CH2:30][O:31][CH2:32]Cl.[C:36]([O:39][CH2:40]C)(=O)[CH3:37]>CN(C)C=O.O>[CH3:1][C:2]1([CH3:24])[CH2:10][C:9]2[N:8]([CH2:32][O:31][CH2:30][CH2:29][Si:28]([CH3:35])([CH3:34])[CH3:27])[N:7]=[C:6]([C:11]3[N:12]([CH2:40][O:39][CH2:36][CH2:37][Si:28]([CH3:34])([CH3:29])[CH3:27])[C:13]4[C:18]([CH:19]=3)=[CH:17][CH:16]=[C:15]([C:20]([O:22][CH3:23])=[O:21])[CH:14]=4)[C:5]=2[CH2:4][CH2:3]1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 136127476methyl 2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)indole-6-carboxylate

Product 1

HCID 58550118methyl 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylateYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Under an argon atmosphere, to a solution of methyl 2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)indole-6-carboxylate (23 g, 71 mmol) in N,N-dimethylformamide (230 ml) was added sodium hydride (6.3 g, 157 mmol) in portions of about 500 mg at an inside temperature of −10° C., and the mixture was stirred for 30 min. Then, 2-(trimethylsilyl)ethoxymethyl chloride (26 g, 157 mmol) was added dropwise over 15 min, and the mixture was further stirred for 2 hr. To the reaction mixture were added ethyl acetate and water, and the organic layer was separated. Then, the organic layer was washed successively with water and saturated brine, and dried over sodium sulfate. Sodium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography to give the title compound (33 g, yield 80%).

Workup

  1. stirringthe mixture was further stirred for 2 hr
  2. customthe organic layer was separated
  3. washThen, the organic layer was washed successively with water and saturated brine
  4. dry with materialdried over sodium sulfate
  5. customSodium sulfate was removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-fdd37e1d38ac4206bc6909a6d35ff89d
Source dataset
uspto-grants-2012_10
Patent number
US08299070B2

Reaction notes

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