Methanol → 3-{4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-one

HRID 2263404Notes

Reaction equation

HRID 2263404 reaction equation
C([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]=[C:14]([C:33]2[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][CH:34]=2)[S:15][C:16]=1[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[NH:29][C:28](=[O:30])[O:27][N:26]=2)=[C:21]([O:31][CH3:32])[CH:20]=1)C1C=CC=CC=1.I[Si](C)(C)C.CO.C(=O)(O)[O-].[Na+]>ClCCl>[OH:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]=[C:14]([C:33]2[CH:34]=[CH:35][C:36]([C:39]([F:40])([F:41])[F:42])=[CH:37][CH:38]=2)[S:15][C:16]=1[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[NH:29][C:28](=[O:30])[O:27][N:26]=2)=[C:21]([O:31][CH3:32])[CH:20]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 85247Trimethylsilyl iodideHCID 516892Sodium BicarbonateHCID 1361499763-{4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-one

Product 1

HCID 1361499373-{4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-oneYield 39.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

118 mg of 3-{4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-one were dissolved in 14 mL of dichloromethane by heating and allowing to cool down to room temperature. To the resulting solution was added 144 μL of iodotrimethylsilane. The resulting mixture was stirred at room temperature for 6.5 h and 6 mL of methanol were added followed by a saturated aqueous solution of sodium bicarbonate. The mixture was stirred for 1 h, filtered and concentrated under reduced pressure. Dichloromethane/water were added to the residue. The organic layer was separated and the aqueous layer extracted three times with dichloromethane. The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (dichloromethane 90/methanol 10) to give 40 mg of 3-{4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-one.

Workup

  1. temperatureby heating
  2. stirringThe mixture was stirred for 1 h
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. additionDichloromethane/water were added to the residue
  6. customThe organic layer was separated
  7. extractionthe aqueous layer extracted three times with dichloromethane
  8. dry with materialThe combined organic extracts were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified by column chromatography on silica gel (dichloromethane 90/methanol 10)

Sources & evidence

ORD record
ord-d40ad7228eb9404d90faf498380a4789
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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