Sodium Bicarbonate → 5-(benzyloxy)-2-(5-[1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl]-1H-pyrrol-2-yl)pyridine

HRID 1882027Notes

Reaction equation

HRID 1882027 reaction equation
[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([CH2:18][CH:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)[C:14](=O)[CH:15]=[CH2:16])=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.[CH2:25]([O:32][C:33]1[CH:34]=[CH:35][C:36]([CH:39]=O)=[N:37][CH:38]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C([O-])(=O)C.[NH4+:45].C(=O)([O-])O.[Na+]>C(O)C.[Cl-].C([N+]1C(C)=C(CCO)SC=1)C1C=CC=CC=1.C(O)(=O)C.O.C(N(CC)CC)C>[CH2:25]([O:32][C:33]1[CH:34]=[CH:35][C:36]([C:39]2[NH:45][C:14]([CH:13]([C:10]3[CH:9]=[CH:8][C:7]([S:4]([CH:1]4[CH2:3][CH2:2]4)(=[O:6])=[O:5])=[CH:12][CH:11]=3)[CH2:18][CH:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)=[CH:15][CH:16]=2)=[N:37][CH:38]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

10

Reactant 4

HCID 516892Sodium BicarbonateHCID 517165Ammonium AcetateHCID 123972545-(Benzyloxy)pyridine-2-carbaldehydeHCID 593312584-[4-(cyclopropylsulfonyl)phenyl]-5-(tetrahydro-2H-pyran-4-yl)pent-1-en-3-one

Product 1

HCID 593314045-(benzyloxy)-2-(5-[1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl]-1H-pyrrol-2-yl)pyridineYield 82%

Reagents, catalysts & solvents 5

HCID 28333523-Benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chlorideCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 4-[4-(cyclopropylsulfonyl)phenyl]-5-(tetrahydro-2H-pyran-4-yl)pent-1-en-3-one (1.56 g) in ethanol (60 mL) were added 5-(benzyloxy)pyridine-2-carbaldehyde (1.00 g), 3-benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium chloride (132 mg) and triethylamine (0.269 mL), and the mixture was heated under reflux for 2 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=20:80-100:0, volume ratio) to give colorless crystals. To a solution of the obtained crystals in acetic acid (40 mL) was added ammonium acetate (3.02 g), and the mixture was stirred at 110° C. for 2 hr. The reaction mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=5:95-50:50, volume ratio) to give the title compound (1.97 g, yield 82%) as a pale-green amorphous solid. MS: 543 (MH+).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed successively with water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=20:80-100:0, volume ratio)
  8. customto give colorless crystals
  9. extractionextracted with ethyl acetate
  10. washThe extract was washed successively with water and saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=5:95-50:50, volume ratio)

Sources & evidence

ORD record
ord-3095e06bfdf24fb1a2908031714fa870
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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