Hydrochloric Acid → [5-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-3-methyl-pent-3-enyl]-phosphonic acid diethyl ester

HRID 32950

Reaktionsgleichung

Reaktionsgleichung von HRID 32950
C([Li])CCC.[CH3:6][P:7](=[O:14])([O:11][CH2:12][CH3:13])[O:8][CH2:9][CH3:10].Br[CH2:16][C:17]([CH3:34])=[CH:18][CH2:19][C:20]1[C:28]([OH:29])=[C:27]2[C:23]([CH2:24][O:25][C:26]2=[O:30])=[C:22]([CH3:31])[C:21]=1[O:32][CH3:33].[Cl-].[NH4+].Cl>C1COCC1.[Cu]I>[CH2:9]([O:8][P:7]([CH2:6][CH2:16][C:17]([CH3:34])=[CH:18][CH2:19][C:20]1[C:28]([OH:29])=[C:27]2[C:23](=[C:22]([CH3:31])[C:21]=1[O:32][CH3:33])[CH2:24][O:25][C:26]2=[O:30])(=[O:14])[O:11][CH2:12][CH3:13])[CH3:10]

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 12685Diethyl methylphosphonateHCID 25517Ammonium ChlorideHCID 670104826-(4-bromo-3-methyl-but-2-enyl)-7-hydroxy-5-methoxy-4-methyl-3H-isobenzofuran-1-oneHCID 178418339Butyllithium

Produkt 1

HCID 76548183[5-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-3-methyl-pent-3-enyl]-phosphonic acid diethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
-60 °C

Versuchsvorschrift

n-Butyl lithium (1.6 M in hexanes, 1 mL) was added to an equal volume of THF at −20° C. A solution of diethyl methylphosphonate (220 mg, 1.45 mmol) in THF (1 mL) was then added dropwise and the solution was stirred for 30 minutes. After cooling at −60° C., the solution was transferred via a cannula to a vial containing copper (I) iodide (276 mg, 1.45 mmol), and the resulting mixture was stirred for 1 hour at −30° C. A solution of 6-(4-bromo-3-methyl-but-2-enyl)-7-hydroxy-5-methoxy-4-methyl-3H-isobenzofuran-1-one 3B (50 mg, 0.15 mmol) in THF (1 mL) was added and the mixture was allowed to warm to 0° C. for 2 hours before saturated aqueous ammonium chloride was added. The reaction mixture was acidified with 2 N HCl and extracted with ethyl acetate. The ethyl acetate extract was concentrated and the residue was chromatographed on silica gel (40% to 100% ethyl acetate/hexanes), affording [5-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-3-methyl-pent-3-enyl]-phosphonic acid diethyl ester 3C as an oil (27 mg, contaminated with the starting diethyl methylphosphonate); 1H NMR (300 MHz, CDCl3) δ 1.32 (m, 6H), 1.8-1.9 (m, 5H), 2.18 (s, 3H), 2.25 (m, 2H), 3.42 (d, J=7.2 Hz, 2H), 3.78 (s, 3H), 4.15 (m, 4H), 5.21 (s, 2H), 5.24 (t, J=7.2 Hz, 1H), 7.65 (s, 1H) ppm.

Aufarbeitung

  1. stirringthe resulting mixture was stirred for 1 hour at −30° C
  2. additionwas added
  3. extractionextracted with ethyl acetate
  4. extractionThe ethyl acetate extract
  5. concentrationwas concentrated
  6. customthe residue was chromatographed on silica gel (40% to 100% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-ca0d9706e4ac4cca8625c2849513458f
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07427636B2

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