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

HRID 906374Notes

Reaction equation

HRID 906374 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

1,1-Dimethylethyl (2S)-4-{[4-(acetylamino)-2-methylphenyl]methyl}-2-methyl-1-piperazinecarboxylate (D53) (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 a total of 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 to give the crude product which was purified by column chromatography. Elution with 0-100% diethyl ether/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, 400 MHz) 6.97 (1H, d), 6.52 (1H, d), 6.46 (1H, dd), 4.17 (1H, br.s), 3.76 (1H, d), 3.57 (2H, br.s), 3.29 (2H, m), 3.01 (1H, td), 2.70 (1H, d), 2.56 (1H, d), 2.30 (3H, s), 2.10 (1H, dd), 1.90 (1H, m), 1.45 (9H, s), 1.18 (3H, d). MS (AP+): 342.3 (MNa+), no molecular (MH+) ion observed.

Workup

  1. temperatureheated for a total of 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. customto give the crude product which
  8. customwas purified by column chromatography
  9. washElution with 0-100% diethyl ether/petroleum ether
  10. customflush with 10% (2M NH3 in MeOH) in DCM

Sources & evidence

ORD record
ord-c7fa052f2aaf4309b9df9a217bf3b841
Source dataset
uspto-grants-2011_09
Patent number
US08012981B2

Reaction notes

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