Hydrogen Bromide → HCID 58452663, compound

HRID 70659Notes

Reaction equation

HRID 70659 reaction equation
Br.[C:2]([C:6]1[CH:11]=[CH:10][C:9](/[C:12](/[C:20]2[CH:25]=[CH:24][C:23]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[C:22]([O:33]C)[N:21]=2)=[CH: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].C(C1C=CC(/C(/C2C=CC=C(OC)N=2)=C\[C@@H]2NC(=O)CC2)=CC=1)(C)(C)C.O>O1CCOCC1>[C:2]([C:6]1[CH:11]=[CH:10][C:9](/[C:12](/[C:20]2[NH:21][C:22](=[O:33])[C:23]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:24][CH:25]=2)=[CH:13]\[C@H:14]2[CH2:15][CH2:16][C:17](=[O:19])[NH:18]2)=[CH:8][CH:7]=1)([CH3:5])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 962WaterHCID 67398957HCID 67398957, compoundHCID 67400114(5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

Product 1

HCID 58452663HCID 58452663, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

48% hydrobromic acid (2 mL) was added to a solution of the mixture of (5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(6-methoxy-5-phenoxypyridin-2-yl)ethenyl]pyrrolidin-2-one and (5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one (61 mg) in 1,4-dioxane (1 mL), and the mixture was stirred at 65° C. for 30 minutes. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, after which the solvent was evaporated under reduced pressure. The residue was purified by preparative HPLC (Waters Sunfire 19×150 mm 5 μm, rate: 20 mL/min, eluent: A=acetonitrile, B=0.1% trifluoroacetic acid solution, gradient: 10 to 90%) and solidified with ethyl acetate-hexane to give the title compound as a colorless amorphous (22 mg, 22% (two steps)). A crude product of (5R)-5-[(E)-2-(4-tert-butylphenyl)-2-(6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one (15 mg) was also obtained.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customafter which the solvent was evaporated under reduced pressure
  5. customThe residue was purified by preparative HPLC (Waters Sunfire 19×150 mm 5 μm, rate

Sources & evidence

ORD record
ord-242eb78fa6964661bf4f182d9cf4b0bc
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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