Tetrabutylammonium Fluoride → (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid {5-[1-(2-hydroxy-ethyl)-5-methyl-1H-pyrazol-3-yl]-2-methyl-phenyl}-amide

HRID 1697882Notes

Reaction equation

HRID 1697882 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C([Si](C)(C)[O:24][CH2:25][CH2:26][N:27]1[C:31]([CH3:32])=[CH:30][C:29]([C:33]2[CH:34]=[CH:35][C:36]([CH3:56])=[C:37]([NH:39][C:40]([C:42]3[C@H:47]([C:48]4[CH:53]=[CH:52][C:51]([F:54])=[CH:50][CH:49]=4)[CH2:46][C:45](=[O:55])[NH:44][CH:43]=3)=[O:41])[CH:38]=2)=[N:28]1)(C)(C)C>C1COCC1>[OH:24][CH2:25][CH2:26][N:27]1[C:31]([CH3:32])=[CH:30][C:29]([C:33]2[CH:34]=[CH:35][C:36]([CH3:56])=[C:37]([NH:39][C:40]([C:42]3[C@H:47]([C:48]4[CH:49]=[CH:50][C:51]([F:54])=[CH:52][CH:53]=4)[CH2:46][C:45](=[O:55])[NH:44][CH:43]=3)=[O:41])[CH:38]=2)=[N:28]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67277422(S)-4-(4-Fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid (5-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-pyrazol-3-yl}-2-methyl-phenyl)-amide

Product 1

HCID 53239311(S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid {5-[1-(2-hydroxy-ethyl)-5-methyl-1H-pyrazol-3-yl]-2-methyl-phenyl}-amideYield 45.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution tetrabutylammonium fluoride (1M in THF) was added drop wise to a 0° C. solution of (S)-4-(4-Fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid (5-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-pyrazol-3-yl}-2-methyl-phenyl)-amide (66 mg) in THF. The mixture was stirred at 0° C. for five minutes and then stirred at room temperature for 18 hours. The mixture was partitioned between water and EtOAc. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated to dryness under reduced pressure. Purification of the crude product by flash chromatography (0 to 8% CH3OH in CH2Cl2) gave 24 mg of (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid {5-[1-(2-hydroxy-ethyl)-5-methyl-1H-pyrazol-3-yl]-2-methyl-phenyl}-amide as a solid, MS (M+H)=419.

Workup

  1. stirringstirred at room temperature for 18 hours
  2. customThe mixture was partitioned between water and EtOAc
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure
  7. customPurification of the crude product by flash chromatography (0 to 8% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-149fde5200004f31b68db31919296133
Source dataset
uspto-grants-2012_04
Patent number
US08163929B2

Reaction notes

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