Potassium Hydroxide → tert-butyl (2S)-4-[(4-amino-2-methylphenyl)methyl]-2-methylpiperazine-1-carboxylate

HRID 2424629Notes

Reaction equation

HRID 2424629 reaction equation
C([NH:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C@@H:14]([CH3:25])[CH2:13]2)=[C:7]([CH3:26])[CH:6]=1)(=O)C.[OH-].[K+]>CO>[NH2:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[C@@H:14]([CH3:25])[CH2:13]2)=[C:7]([CH3:26])[CH:6]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 592621441,1-Dimethylethyl (2S)-4-{[4-(acetylamino)-2-methylphenyl]methyl}-2-methyl-1-piperazinecarboxylate

Product 1

HCID 59262126tert-butyl (2S)-4-[(4-amino-2-methylphenyl)methyl]-2-methylpiperazine-1-carboxylateYield 52.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
140 °C

Procedure

D6 (497 mg, 1.4 mmol) and KOH (1M aq soln., 5 mL) were combined in MeOH (5 mL) and heated to 140° C. for 1 h in a microwave reactor. The reaction mixture was diluted with MeOH (5 mL) and heated for 4 h 55 minutes at 130° C. in the microwave. The reaction mixture was concentrated to remove the MeOH and partitioned between DCM and water. The organic layer was dried and concentrated. The crude product was purified by chromatography. Elution with 0-100% Et2O/petroleum ether followed by a column flush with 10% (2M NH3 in MeOH) in DCM yielded the title compound as a yellow oil (233 mg). δH (CDCl3, 250 MHz) 6.96 (1H, d), 6.52 (1H, d), 6.46 (1H, dd), 4.17 (1H, br.s), 3.76 (1H, m), 3.57 (2H, br.s), 3.29 (2H, AB), 3.01 (1H, td), 2.70 (1H, m), 2.56 (1H, m), 2.29 (3H, s), 2.10 (1H, dd), 1.90 (1H, td), 1.45 (9H, s), 1.18 (3H, d). MS (ES+): MNa+ 342.3, no molecular ion (MH+) observed.

Workup

  1. temperatureheated for 4 h 55 minutes at 130° C. in the microwave
  2. concentrationThe reaction mixture was concentrated
  3. customto remove the MeOH
  4. custompartitioned between DCM and water
  5. customThe organic layer was dried
  6. concentrationconcentrated
  7. customThe crude product was purified by chromatography
  8. washElution with 0-100% Et2O/petroleum ether
  9. customflush with 10% (2M NH3 in MeOH) in DCM

Sources & evidence

ORD record
ord-cbebbbd422814a5f99d5bb0d06a41606
Source dataset
uspto-grants-2011_06
Patent number
US07964597B2

Reaction notes

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