Diisopropylethylamine → 1,1-Dimethylethyl (2S)-4-[(2-chloro-4-nitrophenyl)methyl]-2-methyl-1-piperazinecarboxylate

HRID 644752Notes

Reaction equation

HRID 644752 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:4]=1[Cl:12].Cl.[CH3:14][C@H:15]1[CH2:20][NH:19][CH2:18][CH2:17][N:16]1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[Cl:12][C:4]1[CH:5]=[C:6]([N+:9]([O-:11])=[O:10])[CH:7]=[CH:8][C:3]=1[CH2:2][N:19]1[CH2:18][CH2:17][N:16]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@@H:15]([CH3:14])[CH2:20]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 30163681-(Bromomethyl)-2-chloro-4-nitrobenzeneHCID 45072182(S)-tert-butyl 2-methylpiperazine-1-carboxylate hydrochloride

Product 1

HCID 592621281,1-Dimethylethyl (2S)-4-[(2-chloro-4-nitrophenyl)methyl]-2-methyl-1-piperazinecarboxylateYield 34.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of crude 1-(bromomethyl)-2-chloro-4-nitrobenzene (D102) (0.391 g), 1,1-dimethylethyl (2S)-2-methyl-1-piperazinecarboxylate hydrochloride (0.407 g, 1.72 mmol) and Hunig's base (0.625 mL, 3.59 mmol) in dry DMF (3 mL) was stirred at room temperature for 10 minutes. The reaction mixture was concentrated to give an orange oil which was dissolved in DCM and washed with water (33 2) and brine, then dried and concentrated to give an orange oil. Purification by column chromatography eluting with 0-30% EtOAc/pentane gave the title compound as a yellow oil (0.199 g). δH (CDCl3, 400 MHz) 8.24 (1H, d), 8.12 (1H, dd), 7.77 (1H, d), 4.24 (1H, br.s), 3.85 (1H, d), 3.63 (2H, s), 3.14 (1H, td), 2.76 (1H, m), 2.59 (1H, m), 2.33 (1H, dd), 2.18 (1H, m), 1.47 (9H, s), 1.28 (3H, d). MS (ES): MH+ 370/372,

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto give an orange oil which
  3. washwashed with water (33 2) and brine
  4. customdried
  5. concentrationconcentrated
  6. customto give an orange oil
  7. customPurification by column chromatography
  8. washeluting with 0-30% EtOAc/pentane

Sources & evidence

ORD record
ord-b8844cb3439a4594b64877dc23f0aa67
Source dataset
uspto-grants-2010_04
Patent number
US07700599B2

Reaction notes

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