3-Bromo-2-fluorobenzaldehyde → HCID 86730400, compound

HRID 871146Notes

Reaction equation

HRID 871146 reaction equation
[Br:1][C:2]1[C:3]([F:10])=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].[CH3:11][O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[Mg]Br>C1COCC1.C(Cl)Cl>[Br:1][C:2]1[C:3]([F:10])=[C:4]([CH:5]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[O:12][CH3:11])[OH:6])[CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 2

HCID 220193613-Bromo-2-fluorobenzaldehydeHCID 178489560HCID 178489560, compound2×

Product 1

HCID 86730400HCID 86730400, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-bromo-2-fluorobenzaldehyde (1.0 g, 4.93 mmol) in THF (21.42 mL) cooled to −78° C. was added (2-methoxyphenyl)magnesium bromide in THF (5.91 mL, 5.91 mmol). The reaction mixture was maintained at −78° C. for at least 1 hr, and then allowed to warm to room temperature. The reaction mixture was cooled to 0° C. and additional (2-methoxyphenyl)magnesium bromide in THF (5.91 mL, 5.91 mmol) was added. The mixture was allowed to warm to room temperature overnight. The reaction was quenched with a saturated aqueous solution of NH4Cl. The reaction mixture was diluted with DCM. The layers were separated and the aqueous phase extracted twice with DCM. The organic extracts were combined, dried over Na2SO4, filtered, and concentrated to afford a yellow residue. The crude material was dissolved in a minimal amount of DCM and purified via silica gel chromatography using an ISCO machine (80 g column, 60 mL/min, 0-0% EtOAc in hexanes over 27 min, tr=19 min) gave the title compound (1.22 g, 3.92 mmol, 80% yield) as a pale yellow liquid. 1H NMR (400 MHz, CD3OD) δ 7.54-7.40 (m, 2H), 7.35-7.23 (m, 2H), 7.09-6.90 (m, 3H), 6.38 (s, 1H), 4.12 (q, J=7.0 Hz, 1H), 3.76 (s, 3H).

Workup

  1. temperatureto warm to room temperature
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. temperatureto warm to room temperature overnight
  4. customThe reaction was quenched with a saturated aqueous solution of NH4Cl
  5. additionThe reaction mixture was diluted with DCM
  6. customThe layers were separated
  7. extractionthe aqueous phase extracted twice with DCM
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford a yellow residue
  12. custompurified via silica gel chromatography
  13. customan ISCO machine (80 g column, 60 mL/min, 0-0% EtOAc in hexanes over 27 min, tr=19 min)

Sources & evidence

ORD record
ord-def49184e90f4f0db7499baea4ad00b9
Source dataset
uspto-grants-2015_03
Patent number
US08969586B2

Reaction notes

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