Methanol → HCID 9932967, compound

HRID 398452Notes

Reaction equation

HRID 398452 reaction equation
[CH:1]1([CH2:6][CH:7]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[C:8]([NH:10][C:11]2[S:12][CH:13]=[C:14]([CH2:16][C:17]([OH:19])=[O:18])[N:15]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:28]O>S(=O)(=O)(O)O>[CH3:28][O:18][C:17](=[O:19])[CH2:16][C:14]1[N:15]=[C:11]([NH:10][C:8](=[O:9])[CH:7]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[CH2:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[S:12][CH:13]=1

Participants

4

Reactant 2

HCID 887MethanolHCID 9954241HCID 9954241, compound

Product 1

HCID 9932967HCID 9932967, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidCatalyst

Conditions

Temperature
25 °C

Procedure

A solution of {2-[3-cyclopentyl-2-(3,4-dichlorophenyl)-propionylamino]-thiazol-4-yl}-acetic acid (prepared as in Example 18, 95.4 mg, 0.223 mmol) in methanol (1.1 mL) was treated with 1 drop of concentrated sulfuric acid. The reaction mixture was heated under reflux for 15 h. The reaction mixture was allowed to cool to 25° C. and then concentrated in vacuo to remove methanol. The resulting residue was diluted with ethyl acetate (100 mL). The organic phase was washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 3/1 hexanes/ethyl acetate) afforded {2-[3-cyclopentyl-2-(3,4-dichlorophenyl)-propionylamino]-thiazol-4-yl}-acetic acid methyl ester (77.2 mg, 78%) as a yellow viscous oil: FAB-HRMS m/e calcd for C20H22Cl2N2O3S (M+H)+ 441.0807, found 441.0804.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 15 h
  3. concentrationconcentrated in vacuo
  4. customto remove methanol
  5. additionThe resulting residue was diluted with ethyl acetate (100 mL)
  6. washThe organic phase was washed with a saturated aqueous sodium chloride solution (1×100 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-95eecf24260a4339aab1194e5a5f0d35
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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