Lithium Chloride → {2-Ethyl-4-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-but-2-enyloxymethyl}-phosphonic Acid Diisopropyl Ester

HRID 272190

Reaction equation

HRID 272190 reaction equation
[CH:1]([O:4][P:5]([CH2:11]Br)(=[O:10])[O:6][CH:7]([CH3:9])[CH3:8])([CH3:3])[CH3:2].[OH:13][CH2:14][C:15]([CH2:38][CH3:39])=[CH:16][CH2:17][C:18]1[C:26]([O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])=[C:25]2[C:21]([CH2:22][O:23][C:24]2=[O:34])=[C:20]([CH3:35])[C:19]=1[O:36][CH3:37].CC(C)([O-])C.[Li+].[Cl-].[Li+]>CN(C=O)C>[CH:1]([O:4][P:5]([CH2:11][O:13][CH2:14][C:15]([CH2:38][CH3:39])=[CH:16][CH2:17][C:18]1[C:26]([O:27][CH2:28][CH2:29][Si:30]([CH3:32])([CH3:33])[CH3:31])=[C:25]2[C:21](=[C:20]([CH3:35])[C:19]=1[O:36][CH3:37])[CH2:22][O:23][C:24]2=[O:34])(=[O:10])[O:6][CH:7]([CH3:9])[CH3:8])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 433294Lithium ChlorideHCID 4366885Diisopropyl bromomethylphosphonate2×HCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)2×HCID 670105826-(3-Hydroxymethyl-pent-2-enyl)-5-methoxy-4-methyl-7-(2-trimethylsilanyl-ethoxy)-3H-isobenzofuran-1-one

Product 1

HCID 76542764{2-Ethyl-4-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-but-2-enyloxymethyl}-phosphonic Acid Diisopropyl EsterYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of bromomethylphosphonate diisopropyl ester (680 mg, 2.62 mmol) and 6-(3-hydroxymethyl-pent-2-enyl)-5-methoxy-4-methyl-7-(2-trimethylsilanyl-ethoxy)-3H-isobenzofuran-1-one (688 mg, 1.75 mmol) in DMF (3 mL) was added lithium t-butoxide (11.0M in THF; 2.6 mL). The reaction was heated at 70° C. for 2 hours. After cooling to ambient temperature, more bromomethylphosphonate diisopropyl ester (680 mg, 2.62 mmol) and lithium t-butoxide (1.0M in THF; 2.6 mL) were added. The reaction mixture was heated at 70° C. for a further hour, cooled, poured into a solution of lithium chloride (5% aqueous) and extracted with ethyl acetate. The organic extract was dried and the product was purified by chromatography on silica gel, eluting with hexane-ethyl acetate to provide 347 mg (35%) of the product as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 0.04 (s, 9H), 1.09 (t, 3H, J=7.5 Hz), 1.20-1.26 (m, 2H), 1.31 (t, 12H, J=6 Hz), 2.18 (s, 3H), 2.29 (q, 2H, J=7.5 Hz), 3.5 (m, 2H), 3.59 (d, 2H, J=8.7 Hz), 3.78 (s, 3H), 3.98 (s, 2H), 4.28-4.35 (m, 2H), 4.6-4.8 (m, 2H), 5.13 (s, 2H), 5.4 (t, 1H, J=7 Hz) ppm; 31P (121.4 MHz, CDCl3) δ 20.26 ppm; MS (m/z) 593.3 [M+Na]+.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. temperatureThe reaction mixture was heated at 70° C. for a further hour
  3. temperaturecooled
  4. extractionextracted with ethyl acetate
  5. extractionThe organic extract
  6. customwas dried
  7. customthe product was purified by chromatography on silica gel
  8. washeluting with hexane-ethyl acetate

Sources & evidence

ORD record
ord-aaaaa1ed5e4a499284a49f98a94d1de7
Source dataset
uspto-grants-2008_11
Patent number
US07452901B2

Linked notes

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