Imidazole → 1-(4-t-Butyldimethylsilyloxymethyl-1,3-thiazol-2-yl)-3-hydroxyazetidine

HRID 891565Notes

Reaction equation

HRID 891565 reaction equation
[OH:1][CH2:2][C:3]1[N:4]=[C:5]([N:8]2[CH2:11][CH:10]([OH:12])[CH2:9]2)[S:6][CH:7]=1.[Si:13](Cl)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].N1C=CN=C1.CO>CN(C)C=O>[Si:13]([O:1][CH2:2][C:3]1[N:4]=[C:5]([N:8]2[CH2:11][CH:10]([OH:12])[CH2:9]2)[S:6][CH:7]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 887MethanolHCID 28928tert-Butyldimethylsilyl chlorideHCID 222430061-(4-Hydroxymethyl-1,3-thiazol-2-yl)-3-hydroxyazetidine

Product 1

HCID 222429501-(4-t-Butyldimethylsilyloxymethyl-1,3-thiazol-2-yl)-3-hydroxyazetidineYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-hydroxymethyl-1,3-thiazol-2-yl)-3-hydroxyazetidine (226.5 mg, 1.22 mmol) (obtained as described in Reference Example 12(1)) in dimethylformamide (11.5 ml) were added t-butyldimethylsilyl chloride (220 mg, 1.46 mmol) and imidazole (120 mg, 1.76 mmol) in an ice bath. The reaction mixture was then brought to room temperature in 10 minutes, and stirred for 5 hours. After checking the completion of the reaction, methanol (2 ml) was added thereto in an ice bath, and then the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The obtained organic layer was washed with 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 n-hexane:ethyl acetate (1:1) as the eluant to afford 1-(4-t-butyldimethylsilyloxymethyl-1,3-thiazol-2-yl)-3-hydroxyazetidine (300.4 mg, yield 82%) as a white solid.

Workup

  1. additionwas added
  2. stirringin an ice bath, and then the reaction mixture was stirred at room temperature for 30 minutes
  3. customThe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution
  4. washThe obtained organic layer was washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-dd4890075004463f9776eee848eb0d02
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

Loading…