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

HRID 1418661Notes

Reaction equation

HRID 1418661 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N+:14]([O-:16])=[O:15])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:11][C:10]([OH:13])([CH3:12])[CH2:9]1.N1C=CN=C1.[Si:22](Cl)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23].O>CN(C)C=O.CCCCCC.C(OCC)C>[Si:22]([O:13][C:10]1([CH3:12])[CH2:9][N:8]([C:7]2[CH:6]=[CH:5][C:4]([N+:14]([O-:16])=[O:15])=[CH:3][C:2]=2[F:1])[CH2:11]1)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]

Participants

7

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 543624403-Fluoro-4-(3-hydroxy-3-methyl-1-azetidinyl)nitrobenzene

Product 1

HCID 538523044-[3-[(Tert-butyldimethylsilyl)oxy]-3-methyl-1-azetidinyl]-3-fluoronitrobenzeneYield 70%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21584099Diethylether hexaneSolvent

Procedure

A solution of 3-fluoro-4-(3-hydroxy-3-methyl-1-azetidinyl)nitrobenzene (1.80 g, 8.0 mmol) in dry N,N-dimethylformamide (15 mL) was cooled to 0° C. with an ice bath and then treated with imidazole (0.572 g, 8.4 mmol) and tert-butyldimethylsilyl chloride (1.30 g, 8.4 mmol) under N2. The reaction mixture was stirred overnight with gradual dissipation of the cooling bath. The reaction mixture was then transferred to a separatory funnel, along with water and 1:1 hexane/diethyl ether. After shaking, the layers were separated and the aqueous phase back-extracted with additional 1:1 hexane/diethyl ether. The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered and concentrated in vacuo to give an oil. Chromatography over silica gel, eluting with 3% diethyl ether/hexane and then 1:1 hexane/ethyl acetate, afforded, after concentration of appropriate fractions, 0.536 g of starting alcohol and 1.90 g (70%) of the title compound as a bright yellow solid with mp 98°-99.5° C. and MS(EI) 340 (M+).

Workup

  1. stirringAfter shaking
  2. customthe layers were separated
  3. extractionthe aqueous phase back-extracted with additional 1:1 hexane/diethyl ether
  4. washThe combined organic extracts were washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give an oil
  9. washChromatography over silica gel, eluting with 3% diethyl ether/hexane
  10. custom1:1 hexane/ethyl acetate, afforded

Sources & evidence

ORD record
ord-18fbadbc74134fb59697e2cacd652a36
Source dataset
uspto-grants-1999_03
Patent number
US05883093

Reaction notes

Loading…