Methyl 3-(bromomethyl)benzoate → HCID 57438395, compound

HRID 1161132Notes

Reaction equation

HRID 1161132 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10]Br)[CH:5]=1.[OH:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][C:18]2[CH:19]=[CH:20][C:15]([CH2:14][OH:13])=[CH:16][CH:17]=2)[CH:5]=1

Participants

6

Reactant 2

HCID 517981Methyl 3-(bromomethyl)benzoateHCID 27347064-(Hydroxymethyl)benzeneboronic acid

Product 1

HCID 57438395HCID 57438395, compoundYield 80.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
85 °C

Procedure

Tetrakis(triphenylphosphine)palladium(0) (550 mg, 0.476 mmol) is added to a mixture of 3-bromomethyl-benzoic acid methyl ester (3.0 g, 13.09 mmol) and 4-(hydroxymethyl)-phenylboronic acid (2.99 g, 19.68 mmol) in a mixture of toluene (125 mL) and 2M sodium carbonate (62 mL). The mixture was degassed, placed under nitrogen and heated at 85° C. for 16 hours. After cooling to room temperature, the mixture is concentrated in vacuo and the black residue is partitioned between saturated sodium bicarbonate and dichloromethane. After the layers are separated, the aqueous layer is extracted two more times with dichloromethane. The combined organic layers are washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash chromatography (20% tetrahydrofuran in hexanes) to give 2.71 g of the title compound as a yellow oil: MS (m/z): 239 (M−OH); 1H NMR (CDCl3) δ 7.92 (m, 2H), 7.42-7.36 (m, 2H), 7.34-7.29 (m, 2H), 7.21 (d, J=8.0 Hz, 2H), 4.69 (s, 2H), 4.05 (s, 2H), 3.93 (s, 3H), 1.79 (s, 1H).

Workup

  1. customThe mixture was degassed
  2. temperatureAfter cooling to room temperature
  3. concentrationthe mixture is concentrated in vacuo
  4. customthe black residue is partitioned between saturated sodium bicarbonate and dichloromethane
  5. customAfter the layers are separated
  6. extractionthe aqueous layer is extracted two more times with dichloromethane
  7. washThe combined organic layers are washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue is purified by flash chromatography (20% tetrahydrofuran in hexanes)

Sources & evidence

ORD record
ord-69aee5730bc547b481503a7a1ca8c1fb
Source dataset
uspto-grants-2010_10
Patent number
US07816523B2

Reaction notes

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