Potassium Carbonate → 5-[4-Difluoromethoxy-2-(3-hydroxymethyl-oxetan-3-ylmethoxy)-3-methoxy-phenyl]-3H-isobenzofuran-1-one

HRID 2171086Notes

Reaction equation

[F:1][CH:2]([F:23])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[C:15](=[O:19])[O:14][CH2:13]3)=[C:6]([OH:20])[C:5]=1[O:21][CH3:22].C(=O)([O-])[O-].[K+].[K+].Br[CH2:31][C:32]1([CH2:36][OH:37])[CH2:35][O:34][CH2:33]1>C(#N)C>[F:23][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[C:15](=[O:19])[O:14][CH2:13]3)=[C:6]([O:20][CH2:31][C:32]2([CH2:36][OH:37])[CH2:35][O:34][CH2:33]2)[C:5]=1[O:21][CH3:22]

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirring solution of 5-(4-(difluoromethoxy)-2-hydroxy-3-methoxyphenyl)isobenzofuran-1(3H)-one (80 mg, 0.25 mmol) in acetonitrile (10 mL), was added potassium carbonate (103.5 mg, 0.75 mmol) and (3-bromomethyl-oxetan-3-yl)-methanol (135.7 mg, 0.75 mmol) and the resultant reaction mixture was heated to 80° C. for 16 h. The reaction mixture was cooled to RT, filtered through celite and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 0-30% ethyl acetate in pet ether) to afford title compound as a solid (30 mg, 28.8%).

Workup

customthe resultant reaction mixture
temperatureThe reaction mixture was cooled to RT
filtrationfiltered through celite
concentrationthe filtrate was concentrated under reduced pressure
customThe residue was purified by column chromatography (silica gel, 0-30% ethyl acetate in pet ether)

Sources & evidence

ORD record: ord-e01c8de02c6e4895aa290037e5a728c3
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09051290B2

Reaction notes

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