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Diisopropylethylamine → 1,1-dimethylethyl (2S)-4-[(3-fluoro-4-nitrophenyl)methyl]-2-methyl-1-piperazinecarboxylate

HRID 644716
Notes
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Reaction equation

HRID 644716 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[C:5]([F:12])[CH:4]=1.CCN(C(C)C)C(C)C.[CH3:22][C@H:23]1[CH2:28][NH:27][CH2:26][CH2:25][N:24]1[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30]>CN(C=O)C>[F:12][C:5]1[CH:4]=[C:3]([CH2:2][N:27]2[CH2:26][CH2:25][N:24]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C@@H:23]([CH3:22])[CH2:28]2)[CH:8]=[CH:7][C:6]=1[N+:9]([O-:11])=[O:10]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27746613-Fluoro-4-nitrobenzyl bromideHCID 10081508tert-Butyl (2S)-2-methylpiperazine-1-carboxylate

Product 1

HCID 592621851,1-dimethylethyl (2S)-4-[(3-fluoro-4-nitrophenyl)methyl]-2-methyl-1-piperazinecarboxylateYield 92.5%

Reagents, catalysts & solvents 1

HCID 6228
Dimethylformamide
Solvent
2×

Procedure

A solution of 4-(bromomethyl)-2-fluoro-1-nitrobenzene (232 mg, 1 mmol) and Hunig's base (0.192 mL, 1.1 mmol) in DMF (3 mL) was treated with 1,1-dimethylethyl (2S)-2-methyl-1-piperazinecarboxylate (200 mg, 1 mmol) in DMF (3 mL) and stirred at room temperature for 20 minutes. The reaction mixture was concentrated, re-dissolved in DCM and washed with water and brine, then dried and concentrated. The crude product was purified by column chromatography. Elution with EtOAc/pentane yielded the title compound as a colourless gum (327 mg). δH (CDCl3, 400 MHz) 8.03 (1H, m), 7.34 (1H, dd), 7.27 (1H, m), 4.22 (1H, br.s), 3.84 (1H, d), 3.58 (1H, d), 3.47 (1H, d), 3.13 (1H, td), 2.72 (1H, m), 2.54 (1H, m), 2.22 (1H, dd), 2.09 (1H, m), 1.46 (9H, s), 1.26 (3H, d) [δvalues corrected for incorrectly referenced TMS at 0.62 ppm on spectrum].

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionre-dissolved in DCM
  3. washwashed with water and brine
  4. customdried
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography
  7. washElution with EtOAc/pentane

Sources & evidence

ORD record
ord-04133d725201435bb2fa3a9e91c09975
Source dataset
uspto-grants-2010_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07700599B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes