Imidazole → HCID 69583505, compound

HRID 891664Notes

Reaction equation

HRID 891664 reaction equation
[OH:1][CH:2]1[CH2:5][N:4]([C:6]2[S:7][CH:8]=[C:9]([C:11](=[O:20])[NH:12][C@H:13]([CH2:18][OH:19])[C@@H:14]([CH3:17])[CH2:15][CH3:16])[N:10]=2)[CH2:3]1.[Si:21](Cl)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22].N1C=CN=C1>CN(C)C=O>[OH:1][CH:2]1[CH2:5][N:4]([C:6]2[S:7][CH:8]=[C:9]([C:11](=[O:20])[NH:12][C@H:13]([CH2:18][O:19][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[C@@H:14]([CH3:17])[CH2:15][CH3:16])[N:10]=2)[CH2:3]1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 69544218HCID 69544218, compound

Product 1

HCID 69583505HCID 69583505, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-hydroxy-1-{4-[(1S,2S)-1-(hydroxymethyl)-2-methylbutylcarbamoyl]-1,3-thiazol-2-yl}azetidine (1.34 g, 4.48 mmol) (obtained as described in Reference Example 38(3)) in dimethylformamide (67 ml) were added t-butyldimethylsilyl chloride (810 mg, 5.37 mmol) and imidazole (527 mg, 5.37 mmol) in an ice bath, and then the reaction mixture was stirred in the ice bath for 2.5 hours. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and 10% aqueous sodium chloride solution. The obtained organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using toluene:acetonitrile (5:1→3:1) as the eluant to afford 3-hydroxy-1-{4-[(1S,2S)-1-(t-butyldimethylsilyloxymethyl)-2-methylbutylcarbamoyl]-1,3-thiazol-2-yl}azetidine (1.35 g, yield 97%) as a pale yellow oil.

Workup

  1. customthe completion of the reaction
  2. customthe reaction mixture was partitioned between ethyl acetate and 10% aqueous sodium chloride solution
  3. washThe obtained organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-6f1ee9a34e7c41fc9b50ca1cfe67c024
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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