2,6-Lutidine → [2-Ethyl-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-but-2-enyl]-phosphonic Acid

HRID 33656

Reaction equation

HRID 33656 reaction equation
Br[CH2:2][C:3]([CH2:26][CH3:27])=[CH:4][CH2:5][C:6]1[C:14]([O:15]CC[Si](C)(C)C)=[C:13]2[C:9]([CH2:10][O:11][C:12]2=[O:22])=[C:8]([CH3:23])[C:7]=1[O:24][CH3:25].C[O:29][P:30]([O:33]C)[O:31]C.C[Si](Br)(C)C.N1C(C)=CC=CC=1C>>[CH2:26]([C:3](=[CH:4][CH2:5][C:6]1[C:14]([OH:15])=[C:13]2[C:9](=[C:8]([CH3:23])[C:7]=1[O:24][CH3:25])[CH2:10][O:11][C:12]2=[O:22])[CH2:2][P:30](=[O:29])([OH:33])[OH:31])[CH3:27]

Participants

5

Reactant 4

HCID 79372,6-LutidineHCID 8472Trimethyl phosphiteHCID 76113BromotrimethylsilaneHCID 670098846-(3-Bromomethyl-pent-2-enyl)-5-methoxy-4-methyl-7-(2-trimethylsilanyl-ethoxy)-3H-isobenzofuran-1-one

Product 1

HCID 67011350[2-Ethyl-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-but-2-enyl]-phosphonic AcidYield 58%

Procedure

A solution of 6-(3-bromomethyl-pent-2-enyl)-5-methoxy-4-methyl-7-(2-trimethylsilanyl-ethoxy)-3H-isobenzofuran-1-one (230 mg, 0.5 mmol) in trimethylphosphite (1.5 mL, 12.75 mmol) was heated to 100° C. for 4 hours. The reaction was worked up by removal of excess trimethylphosphite under reduced pressure. The residue was dissolved in acetonitrile (1 mL) and TMSBr (646 μL, 5.0 mmol) and 2,6-lutidine (580 μL, 5.0 mmol) were added at 0° C. The reaction solution was allowed to warm to room temperature and stirred for 4 hours. The reaction was cooled to 0° C. and quenched with addition of MeOH. The reaction mixture was dried under reduced pressure and the residue was purified by RP HPLC using a C18 column with a gradient of H2O, 0.1% TFA-acetonitrile, 0.1% TFA to provide 77 mg (58%) of the product. 1H NMR (300 MHz, CD3OD) δ 1.08 (t, 3H), 2.16 (s, 3H), 2.43 (m, 2H), 2.48 (d, 2H, J=22 Hz), 3.46 (t, 2H, J=6 Hz), 3.79 (s, 3H), 5.25 (s, 2H), 5.38 (q, 1H, J=7 Hz) ppm.; 31P (121.4 MHz, CD3OD) δ 25.65 ppm.; MS (m/z) 355 [M−H]−, 357 [M+H]+.

Workup

  1. customThe reaction was worked up by removal of excess trimethylphosphite under reduced pressure
  2. dissolutionThe residue was dissolved in acetonitrile (1 mL)
  3. temperatureThe reaction was cooled to 0° C.
  4. customquenched with addition of MeOH
  5. customThe reaction mixture was dried under reduced pressure
  6. customthe residue was purified by RP HPLC

Sources & evidence

ORD record
ord-efc4e3ec405b47248deb9724a27d6651
Source dataset
uspto-grants-2008_09
Patent number
US07429565B2

Linked notes

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