Water → HCID 67398498, compound

HRID 70622Notes

Reaction equation

HRID 70622 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Li+].S1C2C=CC=CC=2N=C1S([CH2:23][C@@H:24]1[NH:28][C:27](=[O:29])[CH2:26][CH2:25]1)(=O)=O.[Si:30]([O:37][C:38]1[CH:43]=[CH:42][C:41]([C:44]([C:46]2[CH:51]=[CH:50][C:49]([Cl:52])=[C:48]([O:53][CH3:54])[N:47]=2)=O)=[CH:40][CH:39]=1)([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31].O>O1CCCC1>[Si:30]([O:37][C:38]1[CH:43]=[CH:42][C:41](/[C:44](/[C:46]2[CH:51]=[CH:50][C:49]([Cl:52])=[C:48]([O:53][CH3:54])[N:47]=2)=[CH:23]\[C@@H:24]2[NH:28][C:27](=[O:29])[CH2:26][CH2:25]2)=[CH:40][CH:39]=1)([C:33]([CH3:35])([CH3:34])[CH3:36])([CH3:31])[CH3:32]

Participants

6

Reactant 4

HCID 962WaterHCID 2733832Lithium HexamethyldisilazideHCID 58452854HCID 58452854, compoundHCID 58452868HCID 58452868, compound

Product 1

HCID 67398498HCID 67398498, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A 1 M solution of lithiumhexamethyldisilazide in tetrahydrofuran (35 mL) was added to a solution of (5R)-5-[(1,3-benzothiazol-2-ylsulfonyl)methyl]pyrrolidin-2-one obtained in Reference Example 3-12 (5.01 g) in tetrahydrofuran (150 mL) at −78° C. in a nitrogen gas stream, and the mixture was stirred at −78° C. for 40 minutes. A solution of (4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)(5-chloro-6-methoxypyridin-2-yl)methanone obtained in Reference Example 1-28 (3.2 g) in tetrahydrofuran (20 mL) was added, and the mixture was stirred at −78° C. for two hours. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with 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=7:3→3:7) to give (5R)-5-[(E)-2-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-(5-chloro-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one as a colorless oil (688 mg, 17%).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at −78° C. for two hours
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with 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=7:3→3:7)

Sources & evidence

ORD record
ord-c98a385b65504848a5e0434059c23f02
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

Loading…