Tetrahydrofuran → HCID 178496575, compound

HRID 2235288Notes

Reaction equation

HRID 2235288 reaction equation
[Br:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][CH:7]2[CH2:11][CH2:10][N:9]([C@H:12]3[CH2:17][CH2:16][C@@H:15]([OH:18])[CH2:14][CH2:13]3)[C:8]2=[O:19])=[C:4]([Cl:22])[CH:3]=1.[H-].[Na+].[CH2:25]1COCC1>>[Br:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][CH:7]2[CH2:11][CH2:10][N:9]([C@H:12]3[CH2:13][CH2:14][C@@H:15]([O:18][CH3:25])[CH2:16][CH2:17]3)[C:8]2=[O:19])=[C:4]([Cl:22])[CH:3]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 178515504HCID 178515504, compound

Product 1

HCID 178496575HCID 178496575, compoundYield 83%

Conditions

Temperature
0 °C

Procedure

Dissolve 3-(4-bromo-2-chloro-benzyl)-1-(cis-4-hydroxy-cyclohexyl)-pyrrolidin-2-one (Example 134) (0.20 g, 0.52 mmol) in THF (10 mL) and cool to 0° C. Add NaH (0.062 g, 1.55 mmol, 60% wt.) and stir the reaction mixture for 1 hour at 0° C. Then add Mel (0.11 g, 0.78 mmol) and continue to stir the reaction mixture overnight until LC-MS shows the starting material has gone. Add water (10 mL) and extract the aqueous layer with EtOAc (3×50 mL). Combine the organic layers and dry with Na2SO4, filter, concentrate and purify by flash column chromatography (silica gel, 20-50% of EtOAc/Hexane) to give 0.17 g (83%) of the title compound as colorless oil: MS (APCI-pos mode) m/z (rel intensity) 400.0 (70), 402.0 (100).

Workup

  1. extractionAdd water (10 mL) and extract the aqueous layer with EtOAc (3×50 mL)
  2. dry with materialCombine the organic layers and dry with Na2SO4
  3. filtrationfilter
  4. concentrationconcentrate
  5. custompurify by flash column chromatography (silica gel, 20-50% of EtOAc/Hexane)

Sources & evidence

ORD record
ord-5a49ddd584cf43c7b2b14c7152e3b238
Source dataset
uspto-grants-2010_05
Patent number
US07713979B2

Reaction notes

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