Methanol → Methyl 2-(chloromethyl)-4-phenoxybenzoate

HRID 1480928Notes

Reaction equation

HRID 1480928 reaction equation
[O:1]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=O)[O:12][CH2:11]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(O)(O)O.C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.S(Cl)([Cl:44])=O.[CH3:46][OH:47]>>[CH3:46][O:47][C:13](=[O:12])[C:14]1[CH:15]=[CH:16][C:8]([O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:9][C:10]=1[CH2:11][Cl:44]

Participants

6

Reactant 5

HCID 887MethanolHCID 7628Boric AcidHCID 13097Triphenylphosphine OxideHCID 24386Thionyl ChlorideHCID 445585805-Phenoxy-2-benzofuran-1(3H)-one

Product 1

HCID 86709143Methyl 2-(chloromethyl)-4-phenoxybenzoate

Procedure

To a solid mixture of 5-phenoxy-3H-isobenzofuran-1-one (65.54 g, 0.29 mol), boric acid (538 mg, 8.7 mmol) and triphenylphosphine oxide (2.42 g, 8.7 mmol) was added thionyl chloride (42.3 mL). The resulting mixture was refluxed overnight. After cooled, methanol (300 mL) was slowly added to the reaction mixture. It was then refluxed for 1 h and concentrated. Residue was partitioned between EtOAc and saturated NaHCO3 solution. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to provide the title compound (87.02 g, 0.31 mol) as an oil. It was used directly to the next reaction without further purification. 1H NMR in CDCl3, δ in ppm: 7.91 (d, 1H, 8.6 Hz), 7.5-6.9 (m, 7H), 5.06 (s, 2H), 3.83 (s, 3H).

Workup

  1. temperatureThe resulting mixture was refluxed overnight
  2. temperatureAfter cooled
  3. temperatureIt was then refluxed for 1 h
  4. concentrationconcentrated
  5. customResidue was partitioned between EtOAc and saturated NaHCO3 solution
  6. washThe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-141f421edc7e4630b4a890b37cbc97cb
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

Loading…