Hydrochloric Acid → N-[(1R)-1-(5-hydroxypyridine-2-yl)ethyl]-2-(4-isopropylphenyl)acetamide

HRID 254705

Reaktionsgleichung

Reaktionsgleichung von HRID 254705
[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([NH:13][C@@H:14]([C:16]2[CH:21]=[CH:20][C:19]([O:22]C)=[CH:18][N:17]=2)[CH3:15])=[O:12])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[C-]#N.[Na+].Cl>CS(C)=O.C(Cl)Cl.O>[OH:22][C:19]1[CH:20]=[CH:21][C:16]([C@H:14]([NH:13][C:11](=[O:12])[CH2:10][C:7]2[CH:6]=[CH:5][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:9][CH:8]=2)[CH3:15])=[N:17][CH:18]=1

Komponenten

7

Edukt 3

HCID 313Hydrochloric AcidHCID 8929Sodium CyanideHCID 247654842-(4-isopropylphenyl)-N-[(1R)-1-(5-methoxypyridin-2-yl)ethyl]acetamide

Produkt 1

HCID 24765483N-[(1R)-1-(5-hydroxypyridine-2-yl)ethyl]-2-(4-isopropylphenyl)acetamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
175 °C

Versuchsvorschrift

2-(4-Isopropylphenyl)-N-[(1R)-1-(5-methoxypyridin-2-yl)ethyl]acetamide (3.8 g, 12.2 mmol) (Example 11) was dissolved in DMSO (20 mL) and transferred to a sealed tube. To this solution was added NaCN (3.6 g, 73.0 mmol) and the mixture was stirred at 175° C. for 16 h. The mixture was cooled to room temperature and diluted with CH2Cl2 (200 mL) and water (100 mL). The pH of the aqueous layer was brought to neutral by the addition of 2N HCl and the layers were separated. The organic layer was washed with water (100 mL) and brine (100 mL), concentrated, and purified by normal phase chromatography (2-10% MeOH/CH2Cl2) to give N-[(1R)-1-(5-hydroxypyridine-2-yl)ethyl]-2-(4-isopropylphenyl)acetamide as a tan solid. 1H NMR (CDCl3, 400 MHz) δ 8.06 (t, J=1.65 Hz, 1H), 7.17 (m, 4H), 7.02 (m, 2H), 6.67 (d, J=7.50 Hz, 1H), 5.03 (quint., J=6.96 Hz, 1H), 3.53 (d, J=2.20 Hz, 2H), 2.88 (sept., J=6.69 Hz, 1H), 1.38 (d, J=6.77 Hz, 3H), 1.23 (d, J=6.95, 6H); MS (Electrospray): m/z 299.3 (M+H).

Aufarbeitung

  1. customtransferred to a sealed tube
  2. temperatureThe mixture was cooled to room temperature
  3. customthe layers were separated
  4. washThe organic layer was washed with water (100 mL) and brine (100 mL)
  5. concentrationconcentrated
  6. custompurified by normal phase chromatography (2-10% MeOH/CH2Cl2)

Quellen und Nachweise

ORD-Eintrag
ord-bfad2ec938b04bb08fe83b3ea9db416a
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07875636B2

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