Sodium Hydroxide → 1-[2-(5-{1-[3-chloro-4-(methylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-1,3-thiazol-5-yl]ethanol

HRID 1882064Notes

Reaction equation

HRID 1882064 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:27][CH:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[C:13](=O)[CH2:14][CH2:15][C:16]([C:18]2[S:19][C:20]([CH:23]([OH:25])[CH3:24])=[CH:21][N:22]=2)=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C([O-])(=O)C.[NH4+:38].[OH-].[Na+]>C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([C:13]2[NH:38][C:16]([C:18]3[S:19][C:20]([CH:23]([OH:25])[CH3:24])=[CH:21][N:22]=3)=[CH:15][CH:14]=2)[CH2:27][CH:28]2[CH2:29][CH2:30][O:31][CH2:32][CH2:33]2)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 517165Ammonium AcetateHCID 593313595-[3-chloro-4-(methylsulfonyl)phenyl]-1-[5-(1-hydroxyethyl)-1,3-thiazol-2-yl]-6-(tetrahydro-2H-pyran-4-yl)hexane-1,4-dione

Product 1

HCID 251069811-[2-(5-{1-[3-chloro-4-(methylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-1,3-thiazol-5-yl]ethanolYield 34%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 5-[3-chloro-4-(methylsulfonyl)phenyl]-1-[5-(1-hydroxyethyl)-1,3-thiazol-2-yl]-6-(tetrahydro-2H-pyran-4-yl)hexane-1,4-dione (0.66 g), ammonium acetate (0.50 g) and acetic acid (5 mL) was stirred at 90° C. for 3 hr. The reaction mixture was neutralized with 8M aqueous sodium hydroxide solution, and extracted with ethyl acetate. The ethyl acetate layer was concentrated, 2M aqueous sodium hydroxide solution (1.5 mL), tetrahydrofuran (4 mL) and methanol (4 mL) were added to the residue, and the mixture was stirred with heating under reflux for 2 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to basic silica gel column chromatography, and the title compound (0.19 g, yield 34%) was obtained as a yellow amorphous solid from a fraction eluted with ethyl acetate. MS: 495 (MH+).

Workup

  1. extractionextracted with ethyl acetate
  2. concentrationThe ethyl acetate layer was concentrated
  3. addition2M aqueous sodium hydroxide solution (1.5 mL), tetrahydrofuran (4 mL) and methanol (4 mL) were added to the residue
  4. stirringthe mixture was stirred
  5. temperaturewith heating
  6. temperatureunder reflux for 2 hr
  7. additionWater was added to the reaction mixture
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe ethyl acetate layer was washed with saturated brine
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-213ccd3ef6ba47dbabfeaf765b659a6d
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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