Acetic Acid → HCID 57736427, compound

HRID 1641750Notes

Reaction equation

HRID 1641750 reaction equation
[Si]([O:18][CH2:19][CH2:20][O:21][CH2:22][NH:23][C:24]([C:26]1[CH:31]=[C:30]([CH3:32])[C:29]([CH:33]([C:44]2[CH:49]=[C:48]([F:50])[CH:47]=[CH:46][C:45]=2[F:51])[S:34]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=2)(=[O:36])=[O:35])=[CH:28][N:27]=1)=[O:25])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[NH4+]>O1CCCC1>[F:51][C:45]1[CH:46]=[CH:47][C:48]([F:50])=[CH:49][C:44]=1[CH:33]([S:34]([C:37]1[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=1)(=[O:36])=[O:35])[C:29]1[C:30]([CH3:32])=[CH:31][C:26]([C:24]([NH:23][CH2:22][O:21][CH2:20][CH2:19][OH:18])=[O:25])=[N:27][CH:28]=1

Participants

6

Reactant 4

HCID 176Acetic Acid3×HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium Fluoride3×HCID 57736459N-[[2-(tert-butyldiphenylsilyloxy)ethoxy]methyl]-5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxamide

Product 1

HCID 57736427HCID 57736427, compoundYield 93.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-[[2-(tert-butyldiphenylsilyloxy)ethoxy]methyl]-5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxamide (56 mg, 0.076 mmol) and acetic acid (5 μl, 0.091 mmol) in tetrahydrofuran (5 ml), tetrabutylammonium fluoride (1 M tetrahydrofuran solution) (91 μl, 0.091 mmol) was added, and the mixture was stirred for 6 hours at room temperature. Acetic acid (5 μl, 0.091 mmol) and tetrabutylammonium fluoride (1 M tetrahydrofuran solution) (91 μl, 0.091 mmol) were further added to the reaction solution, and the mixture was stirred for 16 hours at room temperature. Acetic acid (5 μl, 0.091 mmol) and tetrabutylammonium fluoride (1 M tetrahydrofuran solution) (91 μl, 0.091 mmol) were further added to the reaction solution, and the mixture was stirred for 5 hours at room temperature. Saturated aqueous ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, subsequently dried over anhydrous sodium sulfate, and filtered, and then the filtrate was concentrated under reduced pressure. The resulting concentration residue was subjected to flash silica gel column chromatography, and the fraction obtained from an elution with 70% ethyl acetate/hexane was concentrated under reduced pressure. Ether was added to the resulting concentration residue to precipitate a solid, and ether was distilled off to obtain the title compound (35 mg, 0.071 mmol, 93%) as a white solid.

Workup

  1. stirringthe mixture was stirred for 16 hours at room temperature
  2. stirringthe mixture was stirred for 5 hours at room temperature
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialsubsequently dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. concentrationThe resulting concentration residue
  9. customthe fraction obtained from an elution with 70% ethyl acetate/hexane
  10. concentrationwas concentrated under reduced pressure
  11. additionEther was added to the resulting concentration residue
  12. customto precipitate a solid, and ether
  13. distillationwas distilled off

Sources & evidence

ORD record
ord-c5e64bbac66641ed8b03cd9c640e84da
Source dataset
uspto-grants-2012_02
Patent number
US08114886B2

Reaction notes

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