2,6-Dichlorobenzaldehyde → HCID 18332487, compound

HRID 2268803Notes

Reaction equation

HRID 2268803 reaction equation
Br[CH2:2][C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1.BrCCBr.[Cu](C#N)C#N.[Cl-].[Li+].B(F)(F)F.CCOCC.[Cl:33][C:34]1[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[C:35]=1[CH:36]=[O:37]>C1COCC1.[Zn].O>[Cl:33][C:34]1[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[C:35]=1[CH:36]([OH:37])[CH2:2][C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1

Participants

10

Reactant 6

HCID 67372,6-DichlorobenzaldehydeHCID 78391,2-DibromoethaneHCID 8000Boron trifluoride etherateHCID 256687Methyl 4-(bromomethyl)benzoateHCID 433294Lithium ChlorideHCID 178418260HCID 178418260, compound

Product 1

HCID 18332487HCID 18332487, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of methyl 4-(bromomethyl)benzoate (2.0 g, 8.7 mmol) in THF (4.4 ml) was added slowly to cut zinc foil (683 mg, 10.44 mmol) which had been activated with 1,2-dibromoethane (80 mg). After 3 h of stirring at room temperature 2 ml of the solution was referred to a solution of copper cyanide (396 mg, 4.4 mmol) and lithium chloride (356 mg, 8.4 mmol) in THF (4 ml) cooled to −78°. This solution was warmed to −20° and then cooled back to −78°. Boron trifluoride etherate (983 μl, 8 mmol) was then added followed by 2,6-dichlorobenzaldehyde (0.56 g, 3.2 mmol) in THF (1 ml). The reaction was stirred for 2 h and then allowed to warm slowly to room temperature. Water (20 ml) was then added and the reaction mixture extracted into EtOAc (3×25 ml) and the combined organics dried (Na2SO4) and evaporated. Purification by column chromatography (SiO2; hexane:EtOAc. 4:1) gave the title compound as a colourless oil (863 mg, 83%). δH (CDCl3) 7.95 (2H, m, ArH), 7.93-7.26 (4H, m, ArH), 7.17-7.12 (1H, m, ArH), 5.73-5.65 (1H, m, CH), 3.91 (3H, s, CO2Me), 3.43 (1H, dd, J 13.5, 8.4 Hz, CHAB4}L ) and 3.28 (1H, dd, J 13.5, 6.3Hz, CHAHB), m/z (ESI, 60V) 325(MH+).

Workup

  1. temperaturecooled to −78°
  2. temperatureThis solution was warmed to −20°
  3. temperaturecooled back to −78°
  4. extractionthe reaction mixture extracted into EtOAc (3×25 ml)
  5. dry with materialthe combined organics dried (Na2SO4)
  6. customevaporated
  7. customPurification by column chromatography (SiO2; hexane:EtOAc. 4:1)

Sources & evidence

ORD record
ord-a664fda3a0914c5f87271b3810e862ba
Source dataset
uspto-grants-2001_12
Patent number
US06329372B1

Reaction notes

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