Acetic Acid → (R)-4-[(1-Methyl-2,2,2-trifluoro-ethylamino)-methyl]-benzonitrile

HRID 1191006Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1191006
C([BH3-])#N.[Na+].[C:5]([C:7]1[CH:14]=[CH:13][C:10]([CH:11]=O)=[CH:9][CH:8]=1)#[N:6].Cl.[CH3:16][C@@H:17]([NH2:22])[C:18]([F:21])([F:20])[F:19].C(O)(=O)C>CO>[CH3:16][C@@H:17]([NH:22][CH2:11][C:10]1[CH:13]=[CH:14][C:7]([C:5]#[N:6])=[CH:8][CH:9]=1)[C:18]([F:21])([F:20])[F:19]

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 660424-CyanobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 44593757(R)-2-Amino-1,1,1-trifluoropropane hydrochloride

Produkt 1

HCID 59828823(R)-4-[(1-Methyl-2,2,2-trifluoro-ethylamino)-methyl]-benzonitrileAusbeute 27,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

Add sodium cyanoborohydride (3.36 g, 53.5 mmol) to a solution of 4-cyanobenzaldehyde (1.75 g, 13.35 mmol) and (R)-1-methyl-2,2,2-trifluoro-ethylamine hydrochloride (2 g, 13.37 mmol) in methanol (17 mL) containing acetic acid (1.53 mL, 26.75 mmol). Stir the mixture at room temperature overnight. Partition the mixture between 1N aqueous NaOH/DCM (1:1, 500 mL) and extract the aqueous layer twice with DCM. Dry the combined organic extracts over MgSO4, concentrate in vacuo and purify by chromatography on silica gel (120 g) eluting with hexane/EtOAc (19:1, 9:1, 85:15 and 4:1) to obtain the desired intermediate (0.83 g, 27%). MS (ES+) m/z: 229 (M+H)+.

Aufarbeitung

  1. customPartition the mixture between 1N aqueous NaOH/DCM (1:1, 500 mL)
  2. extractionextract the aqueous layer twice with DCM
  3. dry with materialDry the combined organic extracts over MgSO4
  4. concentrationconcentrate in vacuo
  5. custompurify by chromatography on silica gel (120 g)
  6. washeluting with hexane/EtOAc (19:1, 9:1, 85:15 and 4:1)

Quellen und Nachweise

ORD-Eintrag
ord-e6d71cbd1e324fadb2d0c77c10a71133
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08680091B2

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