Hydrogen Bromide → HCID 58452638, compound

HRID 70627Notes

Reaction equation

HRID 70627 reaction equation
Br.[C:2]([C:6]1[CH:11]=[CH:10][C:9]([CH:12]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([O:27]C)[N:21]=2)[CH2:13][C@@H:14]2[NH:18][C:17](=[O:19])[CH2:16][CH2:15]2)=[CH:8][CH:7]=1)([CH3:5])([CH3:4])[CH3:3]>O1CCOCC1>[C:2]([C:6]1[CH:7]=[CH:8][C:9]([CH:12]([C:20]2[NH:21][C:22](=[O:27])[C:23]([Cl:26])=[CH:24][CH:25]=2)[CH2:13][C@H:14]2[CH2:15][CH2:16][C:17](=[O:19])[NH:18]2)=[CH:10][CH:11]=1)([CH3:5])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 67398525HCID 67398525, compound

Product 1

HCID 58452638HCID 58452638, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

48% hydrobromic acid (1 mL) was added to a solution of (5R)-5-[2-(4-tert-butylphenyl)-2-(5-chloro-6-methoxypyridin-2-yl)ethyl]pyrrolidin-2-one (100 mg) in 1,4-dioxane (2 mL), and the mixture was stirred at room temperature for 30 minutes and at 65° C. for 30 minutes. The reaction solution was extracted 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 resulting residue was purified by preparative TLC (chloroform:methanol=10:1) to give 6-{1-(4-tert-butylphenyl)-2-[(2R)-5-oxopyrrolidin-2-yl]ethyl}-3-chloropyridin-2(1H)-one, which was separated by preparative HPLC (Inertsil ODS-3 (20 mm i.d.×250 mm L, GL Sciences Inc.), 40° C., flow rate: 10 mL/min, acetonitrile:water=40:60). The fraction containing a single diastereomer eluted with a retention time of 43 minutes was concentrated to give the title compound as a white solid (18 mg, 19%) (Example 4-69).

Workup

  1. extractionThe reaction solution was extracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customThe solvent was then evaporated under reduced pressure
  6. customThe resulting residue was purified by preparative TLC (chloroform:methanol=10:1)

Sources & evidence

ORD record
ord-7d034317969a49c39cbbcc60db912dec
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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