N-bromobutanimide → HCID 68153680, compound

HRID 1405367Notes

Reaction equation

HRID 1405367 reaction equation
[CH3:1][N:2]1[C:10]2([CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:17])[CH2:12][CH2:11]2)[C:6]2=[CH:7][CH:8]=[CH:9][N:5]2[CH2:4][CH2:3]1.C1C(=O)N([Br:33])C(=O)C1>C(Cl)Cl>[Br:33][C:9]1[N:5]2[CH2:4][CH2:3][N:2]([CH3:1])[C:10]3([CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)=[O:17])[CH2:12][CH2:11]3)[C:6]2=[CH:7][CH:8]=1

Participants

4

Reactant 2

HCID 67184N-bromobutanimide2×HCID 68153686HCID 68153686, compound

Product 1

HCID 68153680HCID 68153680, compoundYield 63.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To benzyl 2-methylspiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-carboxylate (3.00 g, 8.84 mmol) in CH2Cl2 (30 mL) at 0° C. was added NBS (1.57 g, 8.84 mmol) portionwise. The reaction mixture was stirred at 0° C. for 2 h. Additional NBS (157 mg) was added and the reaction mixture was stirred at 0° C. for 15 minutes (repeated 6 additional times until starting material was consumed). The reaction mixture was diluted with 0.5 M Na2S2O3 (30 mL) and the aqueous phase was removed. The organic phase was washed with brine (30 mL). The organic layer was dried over sodium sulfate, filtered and the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography utilizing a gradient of 0-30% ethyl acetate in CH2Cl2 to yield benzyl 6-bromo-2-methyl-spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-carboxylate (2.34 g, 63%) as a cream solid. ESI-MS m/z calc. 417.1, found 418.1 (M+1)+; Retention time: 1.49 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 7.43-7.26 (m, 5H), 6.09 (d, J=3.7 Hz, 1H), 5.99 (d, J=3.7 Hz, 1H), 5.08 (s, 2H), 3.89-3.74 (m, 2H), 3.68 (t, J=5.8 Hz, 2H), 3.27 (t, J=5.8 Hz, 2H), 3.22-2.99 (m, 2H), 2.21 (s, 3H), 2.09-1.94 (m, 2H), 1.73-1.52 (m, 2H).

Workup

  1. stirringthe reaction mixture was stirred at 0° C. for 15 minutes
  2. custom(repeated 6 additional times until starting material was consumed)
  3. additionThe reaction mixture was diluted with 0.5 M Na2S2O3 (30 mL)
  4. customthe aqueous phase was removed
  5. washThe organic phase was washed with brine (30 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was evaporated under reduced pressure
  9. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-cc4400fc2f4041668d3ef321bb3bf3a4
Source dataset
uspto-grants-2014_12
Patent number
US08916565B2

Reaction notes

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