Tetrabutylammonium Fluoride → HCID 9828695, compound

HRID 726753Notes

Reaction equation

HRID 726753 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH:19]1([O:24][C:25]2[CH:26]=[C:27]([C@@H:33]([C:41]3[CH:46]=[CH:45][C:44]([C:47]([O:56]COCC[Si](C)(C)C)([C:52]([F:55])([F:54])[F:53])[C:48]([F:51])([F:50])[F:49])=[CH:43][CH:42]=3)[CH2:34][C:35]3[CH:40]=[CH:39][N:38]=[CH:37][CH:36]=3)[CH:28]=[CH:29][C:30]=2[O:31][CH3:32])[CH2:23][CH2:22][CH2:21][CH2:20]1>C1COCC1>[CH:19]1([O:24][C:25]2[CH:26]=[C:27]([C@@H:33]([C:41]3[CH:46]=[CH:45][C:44]([C:47]([OH:56])([C:52]([F:53])([F:54])[F:55])[C:48]([F:49])([F:50])[F:51])=[CH:43][CH:42]=3)[CH2:34][C:35]3[CH:36]=[CH:37][N:38]=[CH:39][CH:40]=3)[CH:28]=[CH:29][C:30]=2[O:31][CH3:32])[CH2:20][CH2:21][CH2:22][CH2:23]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86751960HCID 86751960, compound

Product 1

HCID 9828695HCID 9828695, compoundYield 87.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1.0M in THF; 30.4 mL, 30.4 mmol) was added dropwise to a solution of (R)-4-{2-(3-cyclopentyloxy4-methoxyphenyl)-2-[4-(2-(2-(trimethylsilyl)ethoxymethoxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]ethyl}pyridine from Step 4 (4.08 g, 6.09 mmol) in THF (50 mL) at room temperature, and the resulting solution was heated to the reflux temperature for 2.5 h, allowed to cool, and 25% aqueous NH4OAc buffer was added. The aqueous layer was extracted with EtOAc (3×), and the combined organics were washed successively with 25% aqueous NH4OAc buffer, water and brine, dried (MgSO4) and concentrated. The residue was purified by column chromatography on silica (EtOAc/hexane 1:1) to afford a white solid subsequently triturated in 1:4 Et2O/hexane to give the title compound (2.87 g, 87%). 1H NMR (400 MHz, acetone-d6) δ 1.50-1.62 (m, 2H), 1.63-1.88 (m, 6H), 3.44 (m, 2H), 3.71 (s, 3H), 4.43 (t, J=8 Hz, 1H), 4.75 (m, 1H), 6.81 (m, 2H), 6.89 (s, 1H), 7.14 (d, J=6 Hz, 2H), 7.44 (s, 1H), 7.51 (d, J=8 Hz, 2H), 7.67 (d, J=8 Hz, 2H), 8.33 (d, J=6 Hz, 2H).

Workup

  1. temperaturethe resulting solution was heated to the reflux temperature for 2.5 h
  2. temperatureto cool
  3. extractionThe aqueous layer was extracted with EtOAc (3×)
  4. washthe combined organics were washed successively with 25% aqueous NH4OAc buffer, water and brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica (EtOAc/hexane 1:1)
  8. customto afford a white solid
  9. customsubsequently triturated in 1:4 Et2O/hexane

Sources & evidence

ORD record
ord-9137748dedf44b0fadb4ddb95a6a8974
Source dataset
uspto-grants-1998_01
Patent number
US05710170

Reaction notes

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