N-bromobutanimide → Tert-butyl 8-bromo-2-methyl-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4'-piperidine]-1'-carboxylate

HRID 1405360Notes

Reaction equation

HRID 1405360 reaction equation
[CH3:1][N:2]1[C:14]2([CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[C:6]2=[CH:7][CH:8]=[C:9]([C:10]([F:13])([F:12])[F:11])[N:5]2[CH2:4][CH2:3]1.C1C(=O)N([Br:34])C(=O)C1>C(#N)C>[Br:34][C:7]1[CH:8]=[C:9]([C:10]([F:11])([F:13])[F:12])[N:5]2[CH2:4][CH2:3][N:2]([CH3:1])[C:14]3([CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[C:6]=12

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 68153221tert-Butyl 2'-methyl-6'-(trifluoromethyl)-3',4'-dihydro-2'H-spiro[piperidine-4,1'-pyrrolo[1,2-a]pyrazine]-1-carboxylate

Product 1

HCID 68153220Tert-butyl 8-bromo-2-methyl-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4'-piperidine]-1'-carboxylateYield 79.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of tert-butyl 2-methyl-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-carboxylate (5.60 g, 15.0 mmol) in acetonitrile (50 mL) was added NBS (2.80 g, 15.8 mmol). The mixture was stirred at room temperature overnight. The solvent was removed and the residue was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over MgSO4 and concentrated to dryness. The crude material was purified by column chromatography (10-20% EtOAc-Hex) to provide tert-butyl 8-bromo-2-methyl-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-carboxylate (5.40 g, 73%) as a light yellow solid. ESI-MS m/z calc. 452.3. found 454.5 (M+1)+; Retention time: 1.60 minutes (3 minute run).

Workup

  1. customThe solvent was removed
  2. customthe residue was partitioned between EtOAc and water
  3. extractionThe aqueous layer was extracted with EtOAc (2×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated to dryness
  7. customThe crude material was purified by column chromatography (10-20% EtOAc-Hex)

Sources & evidence

ORD record
ord-79c61e4026a14b7d8283e01cdbb189cb
Source dataset
uspto-grants-2014_12
Patent number
US08916565B2

Reaction notes

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