Dimethylformamide → 2-Fluoro-5-(2-methyl-1,3-dioxolan-2-yl)benzaldehyde

HRID 2105083Notes

Reaction equation

HRID 2105083 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2([CH3:14])[O:13][CH2:12][CH2:11][O:10]2)[CH:5]=[CH:6][C:7]=1[F:8].[Li]CCCC.CN([CH:23]=[O:24])C>C1COCC1>[F:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2([CH3:14])[O:13][CH2:12][CH2:11][O:10]2)=[CH:3][C:2]=1[CH:23]=[O:24]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 11129071HCID 11129071, compoundHCID 178418339Butyllithium

Product 1

HCID 578039302-Fluoro-5-(2-methyl-1,3-dioxolan-2-yl)benzaldehydeYield 68.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Intermediate 416.1 (1 g, 3.83 mmol) in THF (20 mL) was cooled to −78° C. before adding 1.6 M n-BuLi (2.63 mL, 4.2 mmol) drop-wise. The reaction was stirred for 10 min before quenching with DMF (0.6 mL, 7.7 mmol) and allowing to warm to rt. The crude reaction mixture was quenched with NH4Cl (10 mL), extracted with EtOAc (3×10 mL), washed organic layer with H2O, brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 100% EtOAc/hexanes gradient) to afford 550 mg of Intermediate 416.2. 1H NMR (400 MHz, CDCl3) δ ppm 1.63 (s, 3H) 3.51-3.92 (m, 2H) 3.90-4.35 (m, 2H) 7.09-7.19 (m, 1H) 7.65-7.79 (m, 1H) 7.99 (dd, J=6.81, 2.42 Hz, 1H) 10.35 (s, 1H).

Workup

  1. customThe crude reaction mixture
  2. customwas quenched with NH4Cl (10 mL)
  3. extractionextracted with EtOAc (3×10 mL)
  4. washwashed organic layer with H2O, brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography (0 to 100% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-a7b5ec46470e42dcbcfdfb70540244e4
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

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