Ammonium Chloride → (5R)-5-{(E)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-[4-(methylsulfanyl)phenyl]ethenyl}pyrrolidin-2-one

HRID 70618Notes

Reaction equation

HRID 70618 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Li+].C1(N2C(S([CH2:25][C@@H:26]3[NH:30][C:29](=[O:31])[CH2:28][CH2:27]3)(=O)=O)=NN=N2)C=CC=CC=1.[CH:32]1([C:35]2[CH:36]=[CH:37][C:38]([C:43]([C:45]3[CH:50]=[CH:49][C:48]([S:51][CH3:52])=[CH:47][CH:46]=3)=O)=[N:39][C:40]=2[O:41][CH3:42])[CH2:34][CH2:33]1.[Cl-].[NH4+]>O1CCCC1>[CH:32]1([C:35]2[CH:36]=[CH:37][C:38](/[C:43](/[C:45]3[CH:46]=[CH:47][C:48]([S:51][CH3:52])=[CH:49][CH:50]=3)=[CH:25]/[C@@H:26]3[NH:30][C:29](=[O:31])[CH2:28][CH2:27]3)=[N:39][C:40]=2[O:41][CH3:42])[CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 58452798HCID 58452798, compoundHCID 58452884HCID 58452884, compound

Product 1

HCID 67400668(5R)-5-{(E)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-[4-(methylsulfanyl)phenyl]ethenyl}pyrrolidin-2-oneYield 8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A 1 M solution of lithiumhexamethyldisilazide in tetrahydrofuran (6.68 mL) was added to a solution of (5R)-5-{[(1-phenyl-1H-tetrazol-5-yl)sulfonyl]methyl}pyrrolidin-2-one obtained in Reference Example 3-2 (1.07 g) in tetrahydrofuran (10 mL) at −78° C. in a nitrogen gas stream, and the mixture was stirred at −78° C. for 30 minutes. A solution of (5-cyclopropyl-6-methoxypyridin-2-yl)[4-(methylsulfanyl)phenyl]methanone obtained in Reference Example 1-51 (500 mg) in tetrahydrofuran (10 mL) was added, and the mixture was stirred at −78° C. for one hour. The reaction solution was poured into a saturated ammonium chloride solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:ethyl acetate=1:2) to give (5R)-5-{(E)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-[4-(methylsulfanyl)phenyl]ethenyl}pyrrolidin-2-one as a colorless oil (50.6 mg, 8%).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at −78° C. for one hour
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with saturated aqueous sodium bicarbonate and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customThe solvent was then evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (chloroform:ethyl acetate=1:2)

Sources & evidence

ORD record
ord-bb2ff79e14774594a405336d3e147727
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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