Hydrogen Bromide → HCID 58452461, compound

HRID 70681Notes

Reaction equation

HRID 70681 reaction equation
Br.[CH:2]1([C:5]2[CH:6]=[CH:7][C:8]([CH:13]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([Cl:28])[CH:22]=3)[CH2:14][C@@H:15]3[NH:19][C:18](=[O:20])[CH2:17][CH2:16]3)=[N:9][C:10]=2[O:11]C)[CH2:4][CH2:3]1.O>O1CCOCC1>[CH:2]1([C:5]2[C:10](=[O:11])[NH:9][C:8]([C@H:13]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([Cl:28])[CH:22]=3)[CH2:14][C@H:15]3[CH2:16][CH2:17][C:18](=[O:20])[NH:19]3)=[CH:7][CH:6]=2)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 962WaterHCID 67397568(5R)-5-[2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(3,4-dichlorophenyl)ethyl]pyrrolidin-2-one

Product 1

HCID 58452461HCID 58452461, 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 (5R)-5-[2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(3,4-dichlorophenyl)ethyl]pyrrolidin-2-one (120 mg) in 1,4-dioxane (4 mL), and the mixture was stirred at 65° C. for one hour. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:0→90:10) to give an (R,S) mixture of the title compound as a brown amorphous (78 mg). This was preparatively isolated by a chiral HPLC column (CHIRALPAK IB, hexane:ethanol=20:80 v/v, 40° C., 10 mL/min, 210 nm) to give 3-cyclopropyl-6-{(1R)-1-(3,4-dichlorophenyl)-2-[(2R)-5-oxopyrrolidin-2-yl]ethyl}pyridin-2(1H)-one as a colorless amorphous (33 mg) and 3-cyclopropyl-6-{(1S)-1-(3,4-dichlorophenyl)-2-[(2R)-5-oxopyrrolidin-2-yl]ethyl}pyridin-2(1H)-one as a colorless amorphous (21 mg).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:0→90:10)
  6. customto give

Sources & evidence

ORD record
ord-4c80b856076a4bed915407836ad594ee
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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