Sodium Carbonate → ethyl 1-(2-benzyloxyethyl)-2-(2,4-bismethoxymethoxyphenyl)-3-cyclohexyl-1H-pyrrolo[2,3-b]pyridine-6-carboxylate

HRID 1012266Notes

Reaction equation

HRID 1012266 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][N:11]1[C:15]2=[N:16][C:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][CH:19]=[C:14]2[C:13]([CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[C:12]1Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:32][O:33][CH2:34][O:35][C:36]1[CH:41]=[C:40]([O:42][CH2:43][O:44][CH3:45])[CH:39]=[CH:38][C:37]=1B(O)O.[Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH2:1]([O:8][CH2:9][CH2:10][N:11]1[C:15]2=[N:16][C:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][CH:19]=[C:14]2[C:13]([CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[C:12]1[C:39]1[CH:38]=[CH:37][C:36]([O:35][CH2:34][O:33][CH3:32])=[CH:41][C:40]=1[O:42][CH2:43][O:44][CH3:45])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 223378172,4-Bis(methoxymethoxy)phenylboronic acidHCID 23152561ethyl 1-(2-benzyloxyethyl)-2-bromo-3-cyclohexyl-1H-pyrrolo[2,3-b]pyridine-6-carboxylate

Product 1

HCID 23152589ethyl 1-(2-benzyloxyethyl)-2-(2,4-bismethoxymethoxyphenyl)-3-cyclohexyl-1H-pyrrolo[2,3-b]pyridine-6-carboxylateYield 99%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

To a suspension of ethyl 1-(2-benzyloxyethyl)-2-bromo-3-cyclohexyl-1H-pyrrolo[2,3-b]pyridine-6-carboxylate (592 mg, 1.22 mmol) and 2,4-bismethoxymethoxyphenylboronic acid (384 mg, 1.59 mmol) obtained in the same manner as in Example 2-1, Step 2 in 1,2-dimethoxyethane (12 ml) and water (6 ml) were added lithium chloride (155 mg, 3.66 mmol), sodium carbonate (388 mg, 3.66 mmol) and tetrakis(triphenylphosphine)palladium (141 mg, 0.12 mmol), and the mixture was stirred with heating at 110° C. for 2.5 hr. The reaction mixture was allowed to cool to room temperature. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=3:1) to give ethyl 1-(2-benzyloxyethyl)-2-(2,4-bismethoxymethoxyphenyl)-3-cyclohexyl-1H-pyrrolo[2,3-b]pyridine-6-carboxylate (727 mg, yield 99%).

Workup

  1. temperatureto cool to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationAfter filtration
  6. customthe solvent was evaporated under reduced pressure
  7. customthe obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-fa6857f87f1c4729b3929011e65583b6
Source dataset
uspto-grants-2011_07
Patent number
US07977331B1

Reaction notes

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