Chlorotrimethylsilane → HCID 67252001, compound

HRID 1798047Notes

Reaction equation

HRID 1798047 reaction equation
C[Si](Cl)(C)C.Br[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].[F:13][C:14]1[CH:21]=[C:20]([O:22][CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[CH:19]=[C:18]([B:29]2[O:33][C:32](C)(C)C(C)(C)[O:30]2)[C:15]=1C=O>C1COCC1.[Zn]>[CH2:11]([O:10][C:8](=[O:9])[CH2:7][CH:32]1[O:33][B:29]([OH:30])[C:18]2[CH:19]=[C:20]([O:22][CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][O:24]3)[CH:21]=[C:14]([F:13])[C:15]1=2)[CH3:12]

Participants

6

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 7748Ethyl bromoacetateHCID 86653971HCID 86653971, compound

Product 1

HCID 67252001HCID 67252001, compoundYield 87.9%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

To a mixture of zinc powder (0.98 g, 15.0 mmol) in anhydrous THF (30 mL) was added TMSCl (0.39 mL, 3.0 mmol) at 40° C. The resulting mixture was stirred at 55° C. for 15 min and then cooled to 37° C. Ethyl 2-bromoacetate (1.35 mL, 12.0 mmol) was added at 37° C. and the reaction mixture was stirred at this temperature for 30 min. To a solution of 2-fluoro-4-(tetrahydro-2H-pyran-2-yloxy)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (1.05 g, 3.0 mmol) in anhydrous THF (40 mL) was added dropwise above prepared solution at −78° C. The reaction was allowed to stir at room temperature for 1.5 h and quenched by addition of aqueous ammonium chloride (20 mL). The resulting mixture was extracted with ethyl acetate (2×50 mL) and the combined organic layers were dried over anhydrous Na2SO4, concentrated in vacuo. The residue was purified by column chromatography (EtOAc/PE=1/3) on silica gel to give the title compound as a yellow solid. (0.89 g, Yield: 87.9%). MS (ESI) m/z=339 [M+H]+.

Workup

  1. temperaturecooled to 37° C
  2. stirringthe reaction mixture was stirred at this temperature for 30 min
  3. customabove prepared solution at −78° C
  4. stirringto stir at room temperature for 1.5 h
  5. customquenched by addition of aqueous ammonium chloride (20 mL)
  6. extractionThe resulting mixture was extracted with ethyl acetate (2×50 mL)
  7. dry with materialthe combined organic layers were dried over anhydrous Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (EtOAc/PE=1/3) on silica gel

Sources & evidence

ORD record
ord-e4bc90be09344c869cf7cf4ea907c6d2
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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