Sodium Bicarbonate → methyl 6-cyclohexyl-5-(3-nitro-2-[2-(tetrahydropyran-2-yloxy)ethoxy]phenyl}-4H-thieno[3,2-b]pyrrole-2-carboxylate

HRID 1442546Notes

Reaction equation

HRID 1442546 reaction equation
Br[C:2]1[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[C:3]=1[O:4][CH2:5][CH2:6][O:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][O:9]1.C(=O)([O-])O.[Na+].[CH:26]1([C:32]2[C:33]3[S:48][C:47]([C:49]([O:51][CH3:52])=[O:50])=[CH:46][C:34]=3[NH:35][C:36]=2B2OC(C)(C)C(C)(C)O2)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1>O.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>[CH:26]1([C:32]2[C:33]3[S:48][C:47]([C:49]([O:51][CH3:52])=[O:50])=[CH:46][C:34]=3[NH:35][C:36]=2[C:2]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[C:3]=2[O:4][CH2:5][CH2:6][O:7][CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][O:9]2)[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 58679063methyl 6-cyclohexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4H-thieno[3,2-b]pyrrole-2-carboxylateHCID 591656922-[2-(2-Bromo-6-nitrophenoxy)ethoxy]tetrahydropyran

Product 1

HCID 58679101methyl 6-cyclohexyl-5-(3-nitro-2-[2-(tetrahydropyran-2-yloxy)ethoxy]phenyl}-4H-thieno[3,2-b]pyrrole-2-carboxylateYield 44%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

To a solution of 2-[2-(2-bromo-6-nitrophenoxy)ethoxy]tetrahydropyran (1.29 g, 3.72 mmol) in water (10 ml) and ethylene glycol dimethyl ether (20 ml) were added sodium hydrogen carbonate (1.23 g, 14.8 mmol) and tetrakis(triphenylphosphine)palladium (430 mg, 0.372 mmol). Methyl 6-cyclohexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4H-thieno[3,2-b]pyrrole-2-carboxylate (1.60 g, 4.10 mmol) obtained in Step 1 was divided in 4 portions and added every 30 min while stirring at 90° C. with heating. After the completion of addition, the mixture was further stirred at 90° C. for 4 hr. The reaction mixture was allowed to cool to room temperature and water was added. The mixture was extracted with ethyl acetate and the organic layer was washed with water and saturated brine in this order, and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=6:1-3:1) to give methyl 6-cyclohexyl-5-{3-nitro-2-[2-(tetrahydropyran-2-yloxy)ethoxy]phenyl}-4H-thieno[3,2-b]pyrrole-2-carboxylate (863 mg, yield 44%).

Workup

  1. additionadded every 30 min
  2. temperaturewith heating
  3. additionAfter the completion of addition
  4. stirringthe mixture was further stirred at 90° C. for 4 hr
  5. temperatureto cool to room temperature
  6. extractionThe mixture was extracted with ethyl acetate
  7. washthe organic layer was washed with water and saturated brine in this order
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationAfter filtration
  10. customthe solvent was evaporated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=6:1-3:1)

Sources & evidence

ORD record
ord-98f60b375997464a89d0e40423b8992a
Source dataset
uspto-grants-2010_02
Patent number
US07659263B2

Reaction notes

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