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1,1-Dimethylethyl (2S)-4-{[4-(acetylamino)-2-methylphenyl]methyl}-2-methyl-1-piperazinecarboxylate → tert-butyl (2S)-4-[(4-amino-2-methylphenyl)methyl]-2-methylpiperazine-1-carboxylate

HRID 644732
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 644732
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
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

4

Edukt 1

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

Produkt 1

HCID 59262126tert-butyl (2S)-4-[(4-amino-2-methylphenyl)methyl]-2-methylpiperazine-1-carboxylateAusbeute 49,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittel2×HCID 14797Potassium HydroxideLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

1,1-Dimethylethyl (2S)-4-{[4-(acetylamino)-2-methylphenyl]methyl}-2-methyl-1-piperazinecarboxylate (D79) (497 mg, 1.4 mmol) in KOH (1M aq soln., 5 mL) and methanol (5 mL) was heated to 140° C. for 1 h in a microwave reactor. The reaction mixture was diluted with methanol (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 methanol and partitioned between DCM and water. The organic layer was dried and concentrated to give the crude product which was purified by chromatography. Elution with 0-100% diethyl ether/petroleum ether followed by a column flush with 10% (2M NH3 in methanol) in DCM yielded the title compound as a yellow oil (223 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+): MNa+ 342.3 (MNa+), no molecular ion (MH+) observed.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated
  2. customto remove the methanol
  3. custompartitioned between DCM and water
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. customto give the crude product which
  7. customwas purified by chromatography
  8. washElution with 0-100% diethyl ether/petroleum ether
  9. customflush with 10% (2M NH3 in methanol) in DCM

Quellen und Nachweise

ORD-Eintrag
ord-bb4b6e1e58cc4f54a97fa038f339865c
Quelldatensatz
uspto-grants-2010_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07700599B2

Notizen zur Reaktion

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