3-Bromo-2-fluorobenzaldehyde → (3-Bromo-2-fluorophenyl)(5-fluoro-2-methoxyphenyl)methanol

HRID 871137Notes

Reaction equation

HRID 871137 reaction equation
[Br:1][C:2]1[C:3]([F:10])=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].[F:11][C:12]1[CH:13]=[CH:14][C:15]([O:20][CH3:21])=[C:16]([Mg]Br)[CH:17]=1>C1COCC1.C(Cl)Cl>[Br:1][C:2]1[C:3]([F:10])=[C:4]([CH:5]([C:14]2[CH:13]=[C:12]([F:11])[CH:17]=[CH:16][C:15]=2[O:20][CH3:21])[OH:6])[CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 2

HCID 220193613-Bromo-2-fluorobenzaldehydeHCID 178491810HCID 178491810, compound2×

Product 1

HCID 86730396(3-Bromo-2-fluorophenyl)(5-fluoro-2-methoxyphenyl)methanolYield 100%

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 (5-fluoro-2-methoxyphenyl)magnesium bromide in THF (11.82 mL, 5.91 mmol). The reaction mixture was maintained at −78° C. for at least 1 hr, then allowed to warm to room temperature. The reaction mixture was then re-cooled to 0° C. and additional (5-fluoro-2-methoxyphenyl) magnesium bromide in THF (11.82 mL, 5.91 mmol) was added. The reaction mixture was allowed to warm to room temperature overnight. The reaction was quenched with a saturated aqueous solution of NH4Cl and diluted with CH2Cl2. The layers were separated and the aqueous phase was extracted with CH2Cl2 (2×). Organics combined, dried over Na2SO4, filtered, and concentrated to afford a yellow residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (80 g column, 60 mL/min, 0-30% EtOAc in hexanes over 20 min, tr=17.5 min) gave the title compound (1.62 g, 4.92 mmol, 100% yield) as a colorless liquid.

Workup

  1. temperatureto warm to room temperature
  2. temperatureThe reaction mixture was then re-cooled to 0° C.
  3. temperatureto warm to room temperature overnight
  4. customThe reaction was quenched with a saturated aqueous solution of NH4Cl
  5. additiondiluted with CH2Cl2
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted with CH2Cl2 (2×)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford a yellow residue
  12. customto be chromatographed
  13. customPurification of the crude material by silica gel chromatography
  14. customan ISCO machine (80 g column, 60 mL/min, 0-30% EtOAc in hexanes over 20 min, tr=17.5 min)

Sources & evidence

ORD record
ord-a4db56870c264aba9c9d501ef1532240
Source dataset
uspto-grants-2015_03
Patent number
US08969586B2

Reaction notes

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