Imidazole → (S)-tert-butyl 4-(3-(2-fluoro-4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

HRID 407956Notes

Reaction equation

HRID 407956 reaction equation
[C:1]([NH:4][NH:5][C:6]([C:8]1[CH:33]=[CH:32][C:11]([O:12][C@H:13]2[CH2:17][CH2:16][N:15]([CH:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)[C:14]2=[O:31])=[C:10]([F:34])[CH:9]=1)=O)(=[O:3])[CH3:2].N1C=CN=C1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrC(Br)(Br)Br>C(Cl)Cl>[F:34][C:10]1[CH:9]=[C:8]([C:6]2[O:3][C:1]([CH3:2])=[N:4][N:5]=2)[CH:33]=[CH:32][C:11]=1[O:12][C@H:13]1[CH2:17][CH2:16][N:15]([CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])[CH2:20][CH2:19]2)[C:14]1=[O:31]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 86688103(S)-tert-butyl 4-(3-(4-(2-acetylhydrazinecarbonyl)-2-fluorophenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

Product 1

HCID 67470584(S)-tert-butyl 4-(3-(2-fluoro-4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylateYield 73.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(S)-tert-butyl 4-(3-(4-(2-acetylhydrazinecarbonyl)-2-fluorophenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (960 mg, 2.01 mmol) was dissolved in CH2Cl2 (20 mL) and cooled to 0° C. under nitrogen. 1H-imidazole (341 mg, 5.02 mmol), triphenylphosphine (1158 mg, 4.41 mmol) and perbromomethane (1464 mg, 4.41 mmol) were added and the reaction was allowed to warm to ambient temperature overnight. The reaction was partitioned between water and EtOAc, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (100% EtOAc) to afford (S)-tert-butyl 4-(3-(2-fluoro-4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (680 mg, 1.48 mmol, 73.6% yield).

Workup

  1. temperatureto warm to ambient temperature overnight
  2. customThe reaction was partitioned between water and EtOAc
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified over silica gel (100% EtOAc)

Sources & evidence

ORD record
ord-eee50b68a00d404db494d13ce8ae0175
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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