Tetrabutylammonium Fluoride → HCID 67999236, compound

HRID 932201Notes

Reaction equation

HRID 932201 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:36][CH2:37][C@@H:38]([N:42]1[C@H:47]([C:48]2[CH:53]=[CH:52][C:51]([Cl:54])=[CH:50][CH:49]=2)[C@@H:46]([C:55]2[CH:60]=[CH:59][CH:58]=[C:57]([Cl:61])[CH:56]=2)[CH2:45][C@@:44]([CH2:63][C:64]([OH:66])=[O:65])([CH3:62])[C:43]1=[O:67])[CH:39]1[CH2:41][CH2:40]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>C1COCC1.C(OCC)(=O)C>[Cl:61][C:57]1[CH:56]=[C:55]([C@@H:46]2[C@@H:47]([C:48]3[CH:53]=[CH:52][C:51]([Cl:54])=[CH:50][CH:49]=3)[N:42]([C@@H:38]([CH:39]3[CH2:40][CH2:41]3)[CH2:37][OH:36])[C:43](=[O:67])[C@:44]([CH2:63][C:64]([OH:66])=[O:65])([CH3:62])[CH2:45]2)[CH:60]=[CH:59][CH:58]=1

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium Fluoride2×HCID 67999791HCID 67999791, compound

Product 1

HCID 67999236HCID 67999236, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of tetrabutylammonium fluoride, (1.0 M in THF, 0.453 mL, 0.453 mmol) was added to a solution of 2-((3R,5R,6S)-1-((S)-2-(tert-butyldiphenylsilyloxy)-1-cyclopropylethyl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl)acetic acid (Example 251, Step E, 108 mg, 0.151 mmol) in THF (4 ml) and the reaction was stirred at ambient temperature for 20 hours. Analysis by LC-MS showed incomplete reaction so an extra 0.225 ml of tetrabutylammonium fluoride solution was added and the reaction was stirred for another 26 hours. The mixture was diluted in ethyl acetate then washed with water and sat. aq. NaCl solution. The organic layer was dried over sodium sulfate and concentrated. Purification by RP-HPLC (Sunfire Prep C18 OBD 10 μm column, gradient elution of 10% MeCN in water to 80% MeCN in water over a 30 min period, where both solvents contain 0.1% TFA) afforded the title compound as a solid.

Workup

  1. additionwas added
  2. stirringthe reaction was stirred for another 26 hours
  3. washthen washed with water and sat. aq. NaCl solution
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customPurification by RP-HPLC (Sunfire Prep
  7. washC18 OBD 10 μm column, gradient elution of 10% MeCN in water to 80% MeCN in water over a 30 min period, where both solvents

Sources & evidence

ORD record
ord-445a364bfb964d1f9dc1969e33393d0c
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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