Benzyl Bromide → Tert-butyl 5-benzyl-2,4-dioxopiperidine-1-carboxylate

HRID 1055941Notes

Reaction equation

HRID 1055941 reaction equation
[O:1]=[C:2]1[CH2:7][C:6](=[O:8])[CH2:5][CH2:4][N:3]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:26](Br)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.OS([O-])(=O)=O.[K+]>C1COCC1>[CH2:26]([CH:5]1[CH2:4][N:3]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C:2](=[O:1])[CH2:7][C:6]1=[O:8])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 4

HCID 7498Benzyl BromideHCID 516920Potassium bisulfateHCID 2733832Lithium HexamethyldisilazideHCID 23730999tert-Butyl 2,4-dioxopiperidine-1-carboxylate

Product 1

HCID 23731000Tert-butyl 5-benzyl-2,4-dioxopiperidine-1-carboxylateYield 35.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of tert-butyl 2,4-dioxopiperidine-1-carboxylate (Ark Pharm, Inc., Libertyville, Ill.; 2.0 g, 9.389 mmol) in THF (1 L) at 20° C. was added LHMDS (1.0M in THF; 23.47 mL, 23.47 mmol) (dropwise), and the resulting mixture was stirred at 20° C. for 30 min. Benzyl bromide (3.1 g, 18.77 mmol) was added, and the resulting mixture was stirred at 20° C. for 1 h. The mixture was neutralized with 10M aq. KHSO4 solution and extracted with EtOAc. The organic extract was dried over Na2SO4, filtered, and concentrated in vacuo to provide crude rac-tert-butyl 5-benzyl-2,4-dioxopiperidine-1-carboxylate (1.0 g) (used without further purification in subsequent transformations): m/z (ESI, +ve) 204.0 [(M+H)-100]+.

Workup

  1. stirringthe resulting mixture was stirred at 20° C. for 1 h
  2. extractionextracted with EtOAc
  3. extractionThe organic extract
  4. dry with materialwas dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ae47981ae2264b7b901efcf53690eaad
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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