Citric Acid → (2S,4R)-1-(tert-butoxycarbonyl)-4-(6-methoxy-3-methylisoquinolin-1-yloxy)pyrrolidine-2-carboxylic acid

HRID 1511473

Reaktionsgleichung

Reaktionsgleichung von HRID 1511473
[C:1]([N:8]1[CH2:15][CH:14]([OH:16])[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CC(C)([O-])C.[K+].Cl[C:24]1[C:33]2[C:28](=[CH:29][C:30]([O:34][CH3:35])=[CH:31][CH:32]=2)[CH:27]=[C:26]([CH3:36])[N:25]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O>[C:4]([O:3][C:1]([N:8]1[CH2:15][C@H:14]([O:16][C:24]2[C:33]3[C:28](=[CH:29][C:30]([O:34][CH3:35])=[CH:31][CH:32]=3)[CH:27]=[C:26]([CH3:36])[N:25]=2)[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])=[O:2])([CH3:7])([CH3:6])[CH3:5]

Komponenten

6

Edukt 4

HCID 311Citric AcidHCID 111389801-(1,1-Dimethylethyl) (2S)-4-hydroxy-1,2-pyrrolidinedicarboxylateHCID 23665647Potassium tert-butoxide2×HCID 578930951-Chloro-6-methoxy-3-methylisoquinoline

Produkt 1

HCID 57893088(2S,4R)-1-(tert-butoxycarbonyl)-4-(6-methoxy-3-methylisoquinolin-1-yloxy)pyrrolidine-2-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel2×

Versuchsvorschrift

N-BOC-4-hydroxy-L-proline (A; 281 mg; 1.21 mmol) was dissolved in dimethylsulfoxide (3 mL) at room temperature then potassium t-butoxide (270 mg; 2.4 mmol) was added. The resulting solution was stirred at room temperature for 2 hours, then cooled to 0° C. A solution of 1-chloro-6-methoxy-3-methylisoquinoline in dimethylsulfoxide (3 mL) was then added dropwise to the cold solution, followed by t-BuOK, and the mixture was allowed to warn to room temperature. The solution was stirred for 16 hours. The reaction mixture was acidified to pH=4 with 5% aq. citric acid. The solution was extracted with ethyl acetate and the organic phase washed with water followed by brine. The organic phase was concentrated under reduced pressure to give (2S,4R)-1-(tert-butoxycarbonyl)-4-(6-methoxy-3-methylisoquinolin-1-yloxy)pyrrolidine-2-carboxylic acid.

Aufarbeitung

  1. temperaturecooled to 0° C
  2. customto warn to room temperature
  3. stirringThe solution was stirred for 16 hours
  4. extractionThe solution was extracted with ethyl acetate
  5. washthe organic phase washed with water
  6. concentrationThe organic phase was concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-c0d6882bdf8740b1b82840f7788649d4
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08211897B2

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