Imidazole → 3-Fluoro-4-triisopropylsilanyloxybenzaldehyde

HRID 130981Notes

Reaction equation

HRID 130981 reaction equation
[CH:1]([Si:4](Cl)([CH:8]([CH3:10])[CH3:9])[CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2].[F:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[OH:21])[CH:16]=[O:17].N1C=CN=C1.C(O)(C(F)(F)F)=O.[Cl-].[NH4+]>CN(C=O)C.C(#N)C.CCOC(C)=O.CCCCCC>[F:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[O:21][Si:4]([CH:8]([CH3:10])[CH3:9])([CH:5]([CH3:7])[CH3:6])[CH:1]([CH3:3])[CH3:2])[CH:16]=[O:17]

Participants

9

Reactant 5

HCID 795ImidazoleHCID 6422Trifluoroacetic acidHCID 25517Ammonium ChlorideHCID 139400Triisopropylsilyl chlorideHCID 5872503-Fluoro-4-hydroxybenzaldehyde

Product 1

HCID 597300273-Fluoro-4-triisopropylsilanyloxybenzaldehydeYield 111.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6342AcetonitrileSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

Add triisopropylsilyl chloride (74.32 g, 0.3855 mol), followed by DMF (25 mL), to a solution of 3-fluoro-4-hydroxybenzaldehyde (45.01 g, 0.3213 mol) and imidazole (43.74 g, 0.6425 mole) in DMF (313 mL) at 25-29° C. in a steady stream over 2 min. Stir for 1 hr at room temperature till the reaction complete as determined by HPLC (Column: 4.6 mm×25 cm Zorbax RX-C8; eluent: 50/50 0.1% TFA:acetonitrile; flow rate 2 mL/min; detector: 230 nm; temperature: 22° C.; injection: 10 μL). Pour the reaction mixture into saturated aqueous ammonium chloride solution (1 L) and extract with ether (3×1 L). Combine the ether layers, wash with brine (2×750 mL) and dried over sodium sulfate. Filter and concentrate to give a yellow oil (106.3 g). Purify the crude oil on 1 kg Merck silica gel grade 60 with 20:1 heptane/ethyl acetate (90.14 g, 94.6%).

Workup

  1. extractionextract with ether (3×1 L)
  2. washCombine the ether layers, wash with brine (2×750 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationFilter
  5. concentrationconcentrate

Sources & evidence

ORD record
ord-4c23000a79f74817a3f2ac54ed2f5a8a
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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