2-Butene, 1,4-dibromo- → 2-(4-Bromo-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

HRID 272127

Reaction equation

HRID 272127 reaction equation
[CH3:1][C:2]1[C:7]2[CH2:8][O:9][C:10](=[O:11])[C:6]=2[C:5]([OH:12])=[C:4]([CH2:13]/[CH:14]=[C:15](/[CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20])\[CH3:16])[C:3]=1[O:23][CH3:24].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Br:35][CH2:36][CH:37]=[CH:38][CH2:39]Br>C1COCC1>[CH3:22][O:21][C:19](=[O:20])[CH:18]([CH2:39][CH:38]=[CH:37][CH2:36][Br:35])[CH2:17][C:15]([CH3:16])=[CH:14][CH2:13][C:4]1[C:5]([OH:12])=[C:6]2[C:7](=[C:2]([CH3:1])[C:3]=1[O:23][CH3:24])[CH2:8][O:9][C:10]2=[O:11]

Participants

5

Reactant 3

HCID 131802-Butene, 1,4-dibromo-HCID 2724254Sodium bis(trimethylsilyl)amideHCID 6478685Methyl (4E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate

Product 1

HCID 670102042-(4-Bromo-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 esterYield 78.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-30 °C

Procedure

To a cooled (−78° C.) solution of mycophenolic acid methyl ester (138 mg, 0.41 mmol) in THF (2.5 mL) was added a THF solution of sodium bis(trimethysilyl)amide (1.0 M, 0.98 mL). After stirring for 30 minutes, a solution of 1,4-dibromo-2-butene (950 mg, 4.1 mmol) in THF (2.5 mL) was added and stirring was continued for 10 min. The resulting mixture was warmed to −30° C. and stored at this temperature for 16 h. The reaction was quenched with saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate to give, after evaporation of the solvent, a residue which was purified by chromatography on silica gel, eluting with ethyl acetate (0% to 40%)/hexanes, affording 2-(4-bromo-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 (150 mg, 78%) as an oil; 1H NMR (300 MHz, CDCl3) δ 1.75 (s, 3H), 2.0-2.4 (m, 8H), 2.62 (m, 1H), 3.37 (d, J=6.6 Hz, 2H), 3.58 (s, 3H), 3.76 (s, 3H), 3.88 (d, J=4.8 Hz, 2H), 5.1-5.3 (m, 3H), 5.67 (brs, 2H), 7.67 (s, 1H).

Workup

  1. stirringstirring
  2. waitwas continued for 10 min
  3. waitstored at this temperature for 16 h
  4. customThe reaction was quenched with saturated aqueous ammonium chloride
  5. extractionThe mixture was extracted with ethyl acetate
  6. customto give
  7. customafter evaporation of the solvent
  8. customa residue which was purified by chromatography on silica gel
  9. washeluting with ethyl acetate (0% to 40%)/hexanes

Sources & evidence

ORD record
ord-5da0d20767cb477c8d8c0133d8137fc8
Source dataset
uspto-grants-2008_11
Patent number
US07452901B2

Linked notes

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