Acetic Acid → 2-Amino-3-hydroxy-3-(pyridin-4-yl)-1-(pyrrolidin-1-yl)propan-1-one, (2R,3S)-

HRID 2065856Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2065856
Cl.Cl.[NH2:3][C@H:4]([C@@H:12]([OH:19])[C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1)[C:5]([N:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:6].CCN(CC)CC.ClC1C=C(C=CC=1Cl)C=O.CC(O)=O.[BH3-]C#N.[Na+]>CO>[NH2:3][C@H:4]([C@@H:12]([OH:19])[C:13]1[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=1)[C:5]([N:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:6]

Komponenten

7

Edukt 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 227103,4-DichlorobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 236585722-Amino-3-hydroxy-3-(pyridin-4-yl)-1-(pyrrolidin-1-yl)propan-1-one, (2R,3S)-dihydrochloride

Produkt 1

HCID 115359902-Amino-3-hydroxy-3-(pyridin-4-yl)-1-(pyrrolidin-1-yl)propan-1-one, (2R,3S)-Ausbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

To a solution of (−)-(2R,3S)-2-amino-3-hydroxy-3-(pyridin-4-yl)-1-(pyrrolidin-1-yl)propan-1-one dihydrochloride Compound 203 (175 mg, 0.57 mmol) and Et3N (175 μL, 1.25 mmol) in MeOH (5 mL) in a 50 mL round bottom flask equipped with a magnetic stirrer and under nitrogen atmosphere was added slowly at RT 3,4-dichlorobenzaldehyde (112 mg, 0.63 mmol). The reaction mixture was stirred at RT for 20 h. Then AcOH (65 μL, 1.15 mmol) and NaBH3CN (50 mg, 0.74 mmol) were added. The reaction mixture was stirred at RT for another 15 h. MeOH was evaporated and EtOAc (100 mL) was added. The organic phase was washed with a mixture of saturated sodium carbonate (5 mL) and brine (20 mL), then with brine (10 mL) and dried over MgSO4, filtered and evaporated. The crude product was purified by column chromatography (SiO2, eluent EtOAc:MeOH=95:5) to give an oil (−)-(2R,3S)-2-amino-3-hydroxy-3-(pyridin-4-yl)-1-(pyrrolidin-1-yl)propan-1-one (182 mg, 81% yield). This free base (182 mg, 0.46 mmol) was dissolved in MeOH (2 mL) at 4° C. and a solution of HCl 0.1 N in isopropanol (10.2 mL, 1.01 mmol) was added. After evaporation at 30° C., a mixture of EtOAc:MeOH=95:5 was added to yield, after evaporation and drying, to (2R,3S)-2-(3,4-dichlorobenzylamino)-3-hydroxy-3-(pyridin-4-yl)-1-(pyrrolidin-1-yl)propan-1-one dihydrochloride Compound 251 as a white solid (208 mg, 78% yield).

Aufarbeitung

  1. stirringThe reaction mixture was stirred at RT for another 15 h
  2. customMeOH was evaporated
  3. additionEtOAc (100 mL) was added
  4. washThe organic phase was washed with a mixture of saturated sodium carbonate (5 mL) and brine (20 mL)
  5. dry with materialwith brine (10 mL) and dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified by column chromatography (SiO2, eluent EtOAc:MeOH=95:5)

Quellen und Nachweise

ORD-Eintrag
ord-a93731b289ed487b899e058f22e9badb
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08288556B2

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