Ethyl Bromide → (alphaR)-alpha-[(1S)-2-(Dimethylamino)-1-methylethyl]-alpha-ethyl-3-methoxybenzenemethanol

HRID 333191

Reaktionsgleichung

Reaktionsgleichung von HRID 333191
[Mg].B(O)(O)[C@H:3]1N(C([C@@H](N)C(C)C)=O)CC[CH2:4]1.CS(O)(=O)=O.C(Br)C.[CH3:25][N:26]([CH3:40])[CH2:27][C@H:28]([CH3:39])[C:29]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([O:37][CH3:38])[CH:32]=1)=[O:30].S([O-])(O)(=O)=O.[NH4+]>C(OCC)C.C(Br)C>[CH3:40][N:26]([CH3:25])[CH2:27][C@H:28]([CH3:39])[C@:29]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([O:37][CH3:38])[CH:32]=1)([OH:30])[CH2:3][CH3:4]

Komponenten

8

Edukt 5

HCID 6332Ethyl BromideHCID 24655Ammonium bisulfateHCID 5462224MagnesiumHCID 11522448Talabostat mesylateHCID 25146676(2S)-3-(Dimethylamino)-1-(3-methoxyphenyl)-2-methyl-1-propanone

Produkt 1

HCID 9942979(alphaR)-alpha-[(1S)-2-(Dimethylamino)-1-methylethyl]-alpha-ethyl-3-methoxybenzenemethanolAusbeute 98 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6332Ethyl BromideKatalysatorHCID 3283Diethyl EtherLösungsmittel2×

Reaktionsbedingungen

Temperatur
5 °C

Versuchsvorschrift

Magnesium turnings (93.57 g, 3.85 mol) were suspended in dry ethyl ether (2 L) in a 10 L double jacket vessel equipped with an electrical impeller stirrer, a gas transition line, Pt100 temperature measuring equipment and an oil based cooling/heating system and ethyl bromide (25 g, 0.23 mol) was added. After the reaction has started further ethyl bromide (438.6 g, 4.02 mol) was added within 90 minutes below a temperature of 35° C. and the reaction mixture was stirred for another hour. The reaction mixture was cooled to 10° C. to 15° C., (S)-3-(dimethylamino)-1-(3-methoxyphenyl)-2-methylpropan-1-one (774.6 g, 3.5 mol, ee 98%) dissolved in diethyl ether (0.8 L) was added and the reaction mixture was stirred for another two hours. The reaction mixture was cooled to 5° C. and aqueous ammonium hydrogensulfate solution (10% by weight, 2 L) was added. The phases were separated and the organic phase was concentrated in vacuo at 40° C. until a pressure of 5 mbar was reached. (2S,3R)-1-(Dimethylamino)-3-(3-methoxyphenyl)-2-methylpentan-3-ol (862.3 g, 98%) was obtained as a colorless oil (ee 98%).

Aufarbeitung

  1. customequipped with an electrical impeller stirrer
  2. additionwas added
  3. additionwas added within 90 minutes below a temperature of 35° C.
  4. temperatureThe reaction mixture was cooled to 10° C. to 15° C.
  5. additionwas added
  6. stirringthe reaction mixture was stirred for another two hours
  7. customThe phases were separated
  8. concentrationthe organic phase was concentrated in vacuo at 40° C. until a pressure of 5 mbar

Quellen und Nachweise

ORD-Eintrag
ord-c0f447a993fb48acaa749e088a203079
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08877974B2

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