Hydrochloric Acid → (2r)-{[(1r)-2-Hydroxy-1-phenylethyl]amino}(1-methylcyclohexyl)acetonitrile

HRID 2377632Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2377632
Cl.[NH2:2][C@@H:3]([C:7]1([CH3:13])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[C:4](O)=O.[C:14]1([C@H:20]([CH2:22][OH:23])N)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C[Si](C#[N:29])(C)C.Cl.[OH-].[Na+]>C(Cl)(Cl)Cl.[Cl-].[Na+].O.C(Cl)Cl>[OH:23][CH2:22][C@H:20]([NH:2][C@H:3]([C:7]1([CH3:13])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[C:4]#[N:29])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 82115Trimethylsilyl cyanideHCID 2724025(R)-beta-aminophenethyl alcoholHCID 57462912(S)-2-Amino-2-(1-methylcyclohexyl)acetic acid hydrochloride

Produkt 1

HCID 57462914(2r)-{[(1r)-2-Hydroxy-1-phenylethyl]amino}(1-methylcyclohexyl)acetonitrileAusbeute 25 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6212ChloroformLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of (2S)-amino(1-methylcyclohexyl)acetic acid hydrochloride (9.3 g, 73.7 mmol) in CHCl3 (700 mL) was added (R)-(−)-2-phenylglycinol (10.1 g, 73.7 mmol). After stirring for 1 h, the mixture was cooled to 0° C. and trimethylsilylcyanide (19.65 mL, 147.4 mmol) was added. The reaction was then warmed to RT and stirred for 2 d. Brine was then added and the mixture was extracted with DCM. The organic layer was dried over MgSO4 and the solvent was removes in vacuo to yield 28 g of crude silylated material. The mixture was then taken up in DCM (250 mL) and stirred vigorously with 4 N HCl (100 mL) for 24 h. The organic layer was then washed with aq. NaHCO3, dried over MgSO4, and the solvent was removed in vacuo to yield 16 g of crude desilylated material. The aqueous layer was then basified with concentrated NaOH and extracted with EtOAc. The organic layer was then dried over MgSO4 and the solvent was removed in vacuo to yield 3.3 g of crude material. The combined crude material was purified on silica (isco, 120 g, 0-30% EtOac/hex) to yield 5.0 g (25%) of (2R)-{[(1R)-2-hydroxy-1-phenylethyl]amino}(1-methylcyclohexyl)acetonitrile.

Aufarbeitung

  1. temperatureThe reaction was then warmed to RT
  2. stirringstirred for 2 d
  3. extractionthe mixture was extracted with DCM
  4. dry with materialThe organic layer was dried over MgSO4
  5. customthe solvent was removes in vacuo
  6. customto yield 28 g of crude
  7. washThe organic layer was then washed with aq. NaHCO3
  8. dry with materialdried over MgSO4
  9. customthe solvent was removed in vacuo
  10. customto yield 16 g of crude
  11. extractionextracted with EtOAc
  12. dry with materialThe organic layer was then dried over MgSO4
  13. customthe solvent was removed in vacuo
  14. customto yield 3.3 g of crude material
  15. customwas purified on silica (isco, 120 g, 0-30% EtOac/hex)

Quellen und Nachweise

ORD-Eintrag
ord-7647a1a7a8554ce4ab99221d112643dd
Quelldatensatz
uspto-grants-2008_12
Patentnummer
US07470664B2

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