Methanol → 2-[4-(Dimethoxy-phosphoryl)-but-2-enyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic Acid

HRID 910494Notes

Reaction equation

HRID 910494 reaction equation
C[O:2][C:3](=[O:34])[CH:4]([CH2:24][CH:25]=[CH:26][CH2:27][P:28]([O:32][CH3:33])([O:30][CH3:31])=[O:29])[CH2:5][C:6]([CH3:23])=[CH:7][CH2:8][C:9]1[C:10]([OH:22])=[C:11]2[C:15](=[C:16]([CH3:20])[C:17]=1[O:18][CH3:19])[CH2:14][O:13][C:12]2=[O:21].O.CO.O[Li].O>C1COCC1>[CH3:31][O:30][P:28]([CH2:27][CH:26]=[CH:25][CH2:24][CH:4]([CH2:5][C:6]([CH3:23])=[CH:7][CH2:8][C:9]1[C:10]([OH:22])=[C:11]2[C:15](=[C:16]([CH3:20])[C:17]=1[O:18][CH3:19])[CH2:14][O:13][C:12]2=[O:21])[C:3]([OH:34])=[O:2])([O:32][CH3:33])=[O:29]

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 168937Lithium hydroxide, monohydrate2×HCID 765461882-[4-(Dimethoxy-phosphoryl)-but-2-enyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic acid methyl ester

Product 1

HCID 765461892-[4-(Dimethoxy-phosphoryl)-but-2-enyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic Acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-[4-(Dimethoxy-phosphoryl)-but-2-enyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic acid methyl ester (460 mg, 0.927 mmol) in a solution of 1:1:2 of H2O, MeOH, THF (8 mL) was stirred with LiOH.H2O (78 mg, 1.86 mmol) at ambient temperature for 12 hours. A second batch of LiOH.H2O (40 mg, 0.952 mmol) was added. The reaction mixture was stirred at room temperature for another 16 hours, after which no further progress was observed. The reaction was quenched by addition of a saturated aqueous solution of NH4Cl. The organic layer was removed in vacuo and the product was extracted with EtOAc from the aqueous layer, which had been acidified by addition of 5 drops of 2 N HCl. The product was further purified by chromatography to provide the desired product. 1H NMR (300 MHz, CDCl3) δ 1.79 (s, 3H), 2.08-2.38 (m, 4H), 2.15 (s, 3H), 2.53 (d, 1H, J=22 Hz), 2.60 (d, 1H, J=22 Hz), 2.57-2.64 (m, 1H), 3.38 (d, 2H, J=7 Hz), 3.72 (d, 6H, J=11 Hz) 3.76 (s, 3H), 5.20 (s, 2H), 5.27 (t, 1H, J=6 Hz), 5.36-5.63 (m, 2H) ppm; 31P (121.4 MHz, CDCl3) δ 30.5 ppm; MS (m/z) 481.2 [M−H]−.

Workup

  1. customThe reaction was quenched by addition of a saturated aqueous solution of NH4Cl
  2. customThe organic layer was removed in vacuo
  3. extractionthe product was extracted with EtOAc from the aqueous layer, which
  4. additionhad been acidified by addition of 5 drops of 2 N HCl
  5. customThe product was further purified by chromatography

Sources & evidence

ORD record
ord-5e9807ba71304c829b954a8fee2bb574
Source dataset
uspto-grants-2011_09
Patent number
US08022083B2

Reaction notes

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