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 272133Notes

Reaction equation

HRID 272133 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 worked up by concentrating the reaction mixture in vacuo and extracting the product from an aqueous 1N HCl solution 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) 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); 31P (121.4 MHz, CDCl3) δ 29.0, 30.1; MS (m/z) 569.2 [M+H]+, 591.3 [M+Na]+.

Workup

  1. concentrationby concentrating the reaction mixture in vacuo
  2. extractionextracting the product from an aqueous 1N HCl solution 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-25c47d27759544a3864936d55f4586b4
Source dataset
uspto-grants-2008_11
Patent number
US07452901B2

Reaction notes

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