Tetrahydrofuran → 3-Bromo-2-methyl-benzoic acid isopropyl ester

HRID 2215974Notes

Reaction equation

HRID 2215974 reaction equation
S(Cl)(Cl)=O.[Br:5][C:6]1[C:7]([CH3:15])=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([OH:11])=[O:10].[CH2:16]1[CH2:20]OC[CH2:17]1>C(Cl)Cl>[CH:16]([O:10][C:9](=[O:11])[C:8]1[CH:12]=[CH:13][CH:14]=[C:6]([Br:5])[C:7]=1[CH3:15])([CH3:20])[CH3:17]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 24386Thionyl ChlorideHCID 27355903-Bromo-2-methylbenzoic Acid

Product 1

HCID 655448293-Bromo-2-methyl-benzoic acid isopropyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Thionyl chloride (6 mL) was added over 1 min to a 0° C. suspension of 3-bromo-2-methyl benzoic acid (2.15 g, 10 mmol) in DCM (10 mL). After 30 min of stirring, THF (5 mL) was added to induce dissolution. The now homogeneous solution was stirred for 24 h at rt and the volatile component were removed in vacuo. A portion of the crude acid chloride was dissolved in dry isopropyl alcohol (10 mL) and pyridine (2 mL) was added. After stirring for 4 h at rt, the volatile components were removed in vacuo. The residue was partitioned between EtOAc (70 mL) and HCl (1M, 30 mL) and the layers were separated. The organic layer was washed with HCl (1M, 10 mL), NaHCO3 (3×20 mL), water (30 mL), brine (30 mL), and was dried over sodium sulfate. Removal of solvent in vacuo yielded the title compound as a light-yellow oil which was used without further purification. 1H-NMR (CDCl3): δ 7.69 (d, 2H, J=7.7 Hz), 7.11 (t, 1H, J=7.9 Hz), 5.26 (heptet, 1H, J=6.3 Hz), 2.63 (s, 3H), 1.39 (d, 6H, J=6.3 Hz).

Workup

  1. dissolutiondissolution
  2. stirringThe now homogeneous solution was stirred for 24 h at rt
  3. customthe volatile component were removed in vacuo
  4. dissolutionA portion of the crude acid chloride was dissolved in dry isopropyl alcohol (10 mL)
  5. additionpyridine (2 mL) was added
  6. stirringAfter stirring for 4 h at rt
  7. customthe volatile components were removed in vacuo
  8. customThe residue was partitioned between EtOAc (70 mL) and HCl (1M, 30 mL)
  9. customthe layers were separated
  10. washThe organic layer was washed with HCl (1M, 10 mL), NaHCO3 (3×20 mL), water (30 mL), brine (30 mL)
  11. dry with materialwas dried over sodium sulfate
  12. customRemoval of solvent in vacuo

Sources & evidence

ORD record
ord-81106429d8e8485eb38d08eaf1126b60
Source dataset
uspto-grants-2006_09
Patent number
US07109354B2

Reaction notes

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