Trimethyl phosphite → [4-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-2-methyl-but-2-enyl]-phosphonic Acid Dimethyl Ester

HRID 272165

Reaction equation

HRID 272165 reaction equation
Br[CH2:2][C:3]([CH3:20])=[CH:4][CH2:5][C:6]1[C:14]([OH:15])=[C:13]2[C:9]([CH2:10][O:11][C:12]2=[O:16])=[C:8]([CH3:17])[C:7]=1[O:18][CH3:19].[CH3:21][O:22][P:23]([O:26]C)[O:24][CH3:25]>>[CH3:21][O:22][P:23]([CH2:2][C:3]([CH3:20])=[CH:4][CH2:5][C:6]1[C:14]([OH:15])=[C:13]2[C:9](=[C:8]([CH3:17])[C:7]=1[O:18][CH3:19])[CH2:10][O:11][C:12]2=[O:16])(=[O:26])[O:24][CH3:25]

Participants

3

Reactant 2

HCID 8472Trimethyl phosphiteHCID 670104826-(4-bromo-3-methyl-but-2-enyl)-7-hydroxy-5-methoxy-4-methyl-3H-isobenzofuran-1-one

Product 1

HCID 75023209[4-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-2-methyl-but-2-enyl]-phosphonic Acid Dimethyl EsterYield 60%

Procedure

A solution of 6-(4-bromo-3-methyl-but-2-enyl)-7-hydroxy-5-methoxy-4-methyl-3H-isobenzofuran-1-one (33 mg, 0.097 mmol) in trimethylphosphite (1.0 mL, 8.5 mmol) was heated to 100° C. for 1 hour, whereupon complete reaction was indicated by LCMS. The reaction was worked up by removal of the excess reagent under reduced pressure and the residue was purified by silica gel chromatography using EtOAc-hexanes (20-100%) to provide 20 mg (60%) of the desired product. 1H NMR (300 MHz, CDCl3) δ 1.90 (s, 3H), 2.09 (s, 3H), 2.48 (d, 2H, J=22 Hz), 3.38 (t, 2H, J=6 Hz), 3.64 (d, 6H, J=11 Hz), 3.72 (s, 3H), 5.14 (s, 2H), 5.33 (q, 1H, J=6 Hz), 7.65 (br s, 1H) ppm; MS (m/z) 371 [M+H]+.

Workup

  1. customThe reaction was worked up by removal of the excess reagent under reduced pressure
  2. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-b7286080303847ac84df2a0c0a1fa760
Source dataset
uspto-grants-2008_11
Patent number
US07452901B2

Linked notes

Loading…