Acetic Acid → HCID 57404717, Verbindung

HRID 1622311Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1622311
Cl.[NH2:2][OH:3].[OH-].[K+].NO.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][C:18]([C:22]([N:24]2[CH2:33][CH2:32][C:31]3[C:26](=[CH:27][CH:28]=[C:29]([C:34](OC)=[O:35])[CH:30]=3)[CH2:25]2)=[O:23])([CH3:21])[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].C(O)(=O)C>CO.CN(C=O)C>[OH:3][NH:2][C:34]([C:29]1[CH:30]=[C:31]2[C:26](=[CH:27][CH:28]=1)[CH2:25][N:24]([C:22]([C:18]1([CH3:21])[CH2:19][CH2:20][N:15]([C:13]([O:12][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:14])[CH2:16][CH2:17]1)=[O:23])[CH2:33][CH2:32]2)=[O:35]

Komponenten

8

Edukt 5

HCID 176Acetic AcidHCID 787HydroxylamineHCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 67979956HCID 67979956, Verbindung

Produkt 1

HCID 57404717HCID 57404717, VerbindungAusbeute 74,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittel3×HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of hydroxylamine hydrochloride (2.0 g, 29 mmol) in methanol (10 mL) was heated at 90° C. under a dry nitrogen atmosphere until homogeneous. To this heated solution was added a solution of potassium hydroxide (2.85 g, 50.8 mmol) in methanol (6 mL). A precipitate formed on mixing. After heating at 90° C. for 30 minutes, the mixture was cooled to rt and the solids were allowed to settle. The resulting solution was assumed to contain 1.7 M hydroxylamine.potassium salt and was carefully removed by syringe to exclude solids. An aliquot of the above solution (1.95 mL, 3.31 mmol) was added to a solution of methyl 2-{[1-(tert-butoxycarbonyl)-4-methylpiperidin-4-yl]carbonyl}-1,2,3,4-tetrahydroisoquinoline-6-carboxylate (138 mg, 0.331 mmol) in methanol (0.5 mL) and DMF (0.5 mL). After stirring for 3 h at rt, excess reagent was quenched by the addition of acetic acid (0.188 mL, 3.31 mmol). The mixture was concentrated to dryness and the residue was twice co-evaporated with toluene. The crude product was purified by preparative HPLC to afford tert-butyl 4-{[6-(hydroxycarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl]carbonyl}-4-methylpiperidine-1-carboxylate (103 mg, 74.5%). LC-MS: (FA) ES+ 418; 1H NMR (400 MHz, DMSO) δ 11.03 (s, 1H), 9.00 (s, 1H), 7.59-7.52 (m, 2H), 7.28 (d, J=8.0 Hz, 1H), 4.71 (s, 2H), 3.79 (t, J=5.8 Hz, 2H), 3.53-3.44 (m, 2H), 3.15-3.03 (m, 2H), 2.83 (t, J=5.4 Hz, 2H), 2.06-1.96 (m, 2H), 1.47-1.39 (m, 2H), 1.37 (s, 9H), 1.24 (s, 3H).

Aufarbeitung

  1. customA precipitate formed
  2. additionon mixing
  3. temperatureAfter heating at 90° C. for 30 minutes
  4. temperaturethe mixture was cooled to rt
  5. custompotassium salt and was carefully removed by syringe
  6. concentrationThe mixture was concentrated to dryness
  7. customThe crude product was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-35db433ea0ac451a8448ce1c08227a2c
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08778931B2

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