Tetrabutylammonium Fluoride → 2-{4-[(1-Ethoxycarbonyl-ethoxy)-methoxy-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 2114200Notes

Reaction equation

HRID 2114200 reaction equation
C[Si](C)(C)CC[O:5][C:6](=[O:49])[CH:7]([CH2:33][CH:34]=[CH:35][CH2:36][P:37]([O:41][CH:42]([C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH3:43])([O:39][CH3:40])=[O:38])[CH2:8][C:9]([CH3:32])=[CH:10][CH2:11][C:12]1[C:13]([O:25]CC[Si](C)(C)C)=[C:14]2[C:18](=[C:19]([CH3:23])[C:20]=1[O:21][CH3:22])[CH2:17][O:16][C:15]2=[O:24].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[CH2:47]([O:46][C:44]([CH:42]([O:41][P:37]([CH2:36][CH:35]=[CH:34][CH2:33][CH:7]([CH2:8][C:9]([CH3:32])=[CH:10][CH2:11][C:12]1[C:13]([OH:25])=[C:14]2[C:18](=[C:19]([CH3:23])[C:20]=1[O:21][CH3:22])[CH2:17][O:16][C:15]2=[O:24])[C:6]([OH:49])=[O:5])([O:39][CH3:40])=[O:38])[CH3:43])=[O:45])[CH3:48]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 765410252-{4-[(1-Ethoxycarbonyl-ethoxy)-methoxy-phosphoryl]-but-2-enyl}-6-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoic acid 2-trimethylsilanyl-ethyl Ester

Product 1

HCID 725636722-{4-[(1-Ethoxycarbonyl-ethoxy)-methoxy-phosphoryl]-but-2-enyl}-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic AcidYield 78.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-{4-[(1-ethoxycarbonyl-ethoxy)-methoxy-phosphoryl]-but-2-enyl}-6-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoic acid 2-trimethylsilanyl-ethyl ester (14 mg, 0.018 mmol) in THF (1 mL) was stirred with a 1M solution of TBAF in THF (55 μL, 0.055 mmol) for 1 hour. The reaction mixture was concentrated, acidified with 1N HCl and extracted with EtOAc. The organic layer was washed with brine and dried. The product was purified by silica gel column chromatography EtOH-EtOAc (0-10%). Further purification was performed by dissolving the product in CH2Cl2 and passing the compound through a 13 mm Acrodisc syringe filter with a 0.45 μm Nylon membrane to provide 8 mg (77%) of the product. 1H NMR (300 MHz, CDCl3) δ 0.92 (t, 3H, J=7 Hz), 1.30 (d, 3H, J=8 Hz), 1.79 (s, 3H), 2.10-2.39 (m, 4H), 2.15 (s, 3H), 2.53 (d, 1H, J=8 Hz), 2.65 (d, 1H, J=22 Hz), 2.68 (d, 1H, J=22 Hz), 3.38 (d, 2H, J=7 Hz), 3.70 and 3.74 (d, 3H, J=11 Hz), 3.76 (s, 3H), 4.07 (m, 2H), 4.96 (dq, 1H, J=7 Hz), 5.20 (s, 2H), 5.27 (br t, 1H, J=7 Hz), 5.33-5.55 (m, 2H), 7.51-7.56 (m, 1H), 7.68-7.74 (m, 1H) ppm; 31P (121.4 MHz, CDCl3) δ 29.0, 30.1 ppm; MS (m/z) 569.2 [M+H]+, 591.3. [M+Na]+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with brine
  4. customdried
  5. customThe product was purified by silica gel column chromatography EtOH-EtOAc (0-10%)
  6. customFurther purification
  7. dissolutionby dissolving the product in CH2Cl2
  8. filtrationfilter with a 0.45 μm Nylon membrane

Sources & evidence

ORD record
ord-b89461f9a5e2405f8fdc957c38b88d77
Source dataset
uspto-grants-2008_10
Patent number
US07432261B2

Reaction notes

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