Imidazole → 4-[3-[(Tert-butyldimethylsilyl)oxy]-1-azetidinyl]-3-fluoronitrobenzene

HRID 1418649Notes

Reaction equation

HRID 1418649 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N+:13]([O-:15])=[O:14])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:11][CH:10]([OH:12])[CH2:9]1.N1C=CN=C1.[Si:21](Cl)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22].CO.C(Cl)(Cl)Cl>CN(C)C=O.O>[Si:21]([O:12][CH:10]1[CH2:9][N:8]([C:7]2[CH:6]=[CH:5][C:4]([N+:13]([O-:15])=[O:14])=[CH:3][C:2]=2[F:1])[CH2:11]1)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]

Participants

7

Reactant 4

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chloride2×HCID 21584188Chloroform methanolHCID 535516781-(2-Fluoro-4-nitrophenyl)azetidin-3-ol

Product 1

HCID 537387084-[3-[(Tert-butyldimethylsilyl)oxy]-1-azetidinyl]-3-fluoronitrobenzeneYield 74.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-fluoro-4-(3-hydroxy-1-azetidinyl)nitrobenzene (5.51 g, 26.0 mmol) in N,N-dimethylformamide (104 mL) under nitrogen was cooled to 0° C. with an ice bath and treated with imidazole (1.86 g, 27.3 mmol) and then tert-butyldimethylsilyl chloride (4.12 g, 27.3 mmol). The reaction mixture was stirred at 0° C. for 30 min and then at room temperature overnight. TLC analysis (5% methanol/chloroform) at this time revealed a small amount of starting material still remained. An additional amount of tert-butyldimethylsilyl chloride (0.392 g) was added. After stirring overnight, TLC analysis indicated the reaction was complete. The reaction mixture was diluted with water (500 mL) and extracted with dichloromethane (4×70 mL). The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to a yellow solid. Chromatography over silica gel (200 g), eluting with 5% and 10% ethyl acetate/hexane, afforded, after concentration of appropriate fractions, 6.30 g (74%) of the title compound as a yellow solid with mp 98.5°-99.5° C. and MS(EI) 326 (M+).

Workup

  1. customat room temperature
  2. customovernight
  3. stirringAfter stirring overnight
  4. extractionextracted with dichloromethane (4×70 mL)
  5. washThe combined organic extracts were washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure to a yellow solid
  9. washChromatography over silica gel (200 g), eluting with 5% and 10% ethyl acetate/hexane
  10. customafforded

Sources & evidence

ORD record
ord-5a74c7e730bd4c4589f2f5b0e0021290
Source dataset
uspto-grants-1999_03
Patent number
US05883093

Reaction notes

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