Acetic Anhydride → N-[2-(7-isopropyl-1,6-dihydro-2H-cyclopenta[d]furo[2,3-b]pyridin-8-yl)ethyl]acetamide

HRID 2389939Notes

Reaction equation

HRID 2389939 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1(O)[C:8]2=[C:9]3[CH2:15][CH2:14][O:13][C:10]3=[N:11][CH:12]=[C:7]2[CH2:6][CH:5]1[CH:16]([CH3:18])[CH3:17].C(N(CC)CC)C.[C:27](OC(=O)C)(=[O:29])[CH3:28].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.S([O-])([O-])(=O)=O.[Mg+2]>O1CCCC1.C(=O)([O-])O.[Na+]>[CH:16]([C:5]1[CH2:6][C:7]2[C:8]([C:4]=1[CH2:3][CH2:2][NH:1][C:27](=[O:29])[CH3:28])=[C:9]1[CH2:15][CH2:14][O:13][C:10]1=[N:11][CH:12]=2)([CH3:18])[CH3:17]

Participants

8

Reactant 5

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 24083Sulfuric acid magnesium salt (1:1)HCID 521998p-Toluenesulfonic acid monohydrateHCID 591793768-(2-aminoethyl)-7-isopropyl-1,6,7,8-tetrahydro-2H-cyclopenta[d]furo[2,3-b]pyridin-8-ol

Product 1

HCID 59179372N-[2-(7-isopropyl-1,6-dihydro-2H-cyclopenta[d]furo[2,3-b]pyridin-8-yl)ethyl]acetamideYield 16%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent2×

Procedure

To a solution of 8-(2-aminoethyl)-7-isopropyl-1,6,7,8-tetrahydro-2H-cyclopenta[d]furo[2,3-b]pyridin-8-ol (214 mg, 0.816 mmol) in tetrahydrofuran (8.2 mL) were added triethylamine (228 μL, 1.63 mmol) and acetic anhydride (92.5 μL, 0.979 mmol) under ice-cooling, and the mixture was stirred for 5 min. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction solution, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→15/85) and dissolved in toluene (10 mL). p-Toluenesulfonic acid monohydrate (478 mg, 2.52 mmol) and magnesium sulfate (900 mg) were added, and the mixture was stirred at 100° C. for 13 hr. The reaction solution was diluted with saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→10/90) to give the title compound (37.4 mg, yield 16%).

Workup

  1. temperaturecooling
  2. customthe solvent was evaporated under reduced pressure
  3. customThe residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→15/85)
  4. dissolutiondissolved in toluene (10 mL)
  5. stirringthe mixture was stirred at 100° C. for 13 hr
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe extract was washed with saturated brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→10/90)

Sources & evidence

ORD record
ord-6db5db304ba045f2b23be3b9b6365315
Source dataset
uspto-grants-2012_09
Patent number
US08273761B2

Reaction notes

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