Hydrochloric Acid → Methyl 4-(4-fluorobenzyl)-3-methoxycarbonylbenzoate

HRID 2187620Notes

Reaction equation

HRID 2187620 reaction equation
[Br-].[F:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][Zn+])=[CH:5][CH:4]=1.Br[C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][C:13]=1[C:22]([O:24][CH3:25])=[O:23].Cl>O1CCCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[F:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][C:20]2[CH:21]=[CH:12][C:13]([C:22]([O:24][CH3:25])=[O:23])=[CH:14][C:15]=2[C:16]([O:18][CH3:19])=[O:17])=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 2824912Dimethyl 4-bromoisophthalateHCID 178505763HCID 178505763, compound

Product 1

HCID 18476032Methyl 4-(4-fluorobenzyl)-3-methoxycarbonylbenzoate

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A 2.OM solution of 4-fluorobenzyl zinc bromide in tetrahydrofuran (95 ml, 190 mmol; Negishi, E-i. and King, A. O., J.O.C.1977,42,1821) was added dropwise over 20 minutes to a stirred solution of dimethyl 4-bromoisophthalate (20.0 g, 73.2 mmol) and tris(dibenzylideneacetone)dipalladium(O) (0.67 g,0.73 mmol) in tetrahydrofuran (270 ml) at ambient temperature under an inert atmosphere. During the addition the internal temperature rose to 40° C. The reaction mixture was stirred for 3 hours and then poured into 2M. HCl (1500 ml), cooled in an ice bath and the product extracted into ethyl acetate (3×700 ml). The extracts were washed with water (500 ml), brine (500 ml), dried, and the solvent evaporated under reduced pressure. The residue was taken up in a small quantity of dichloromethane, isohexane added, and the solid which crystallised from the solution, filtered and dried to give methyl 4-(4-fluorobenzyl)-3-methoxycarbonylbenzoate (10.5 g)

Workup

  1. additionDuring the addition the internal temperature
  2. customrose to 40° C
  3. additionpoured into 2M
  4. extractionthe product extracted into ethyl acetate (3×700 ml)
  5. washThe extracts were washed with water (500 ml), brine (500 ml)
  6. customdried
  7. customthe solvent evaporated under reduced pressure
  8. additionadded
  9. customthe solid which crystallised from the solution
  10. filtrationfiltered
  11. customdried

Sources & evidence

ORD record
ord-a735db8a0cd6486a8bab4dd3323ed27f
Source dataset
uspto-grants-2002_06
Patent number
US06410539B1

Reaction notes

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