Methanol → t-butyl 4-[2-(4-cyano-2-fluoro-5-methoxyphenoxy)ethyl]-5-cyclopropyl-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate

HRID 516262Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 516262
F[C:2]1[CH:9]=[C:8](F)[C:7]([F:11])=[CH:6][C:3]=1[C:4]#[N:5].[CH:12]1([C:15]2[C:25]3[CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21][CH2:20][C:19]=3[CH:18]=[C:17]3[O:33][CH2:34][CH2:35][N:36]([CH2:37][CH2:38][OH:39])[C:16]=23)[CH2:14][CH2:13]1.C[C:41](C)([O-:43])C.[K+].CO>C1COCC1.C(OCC)(=O)C>[C:4]([C:3]1[C:2]([O:43][CH3:41])=[CH:9][C:8]([O:39][CH2:38][CH2:37][N:36]2[C:16]3=[C:15]([CH:12]4[CH2:13][CH2:14]4)[C:25]4[CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21][CH2:20][C:19]=4[CH:18]=[C:17]3[O:33][CH2:34][CH2:35]2)=[C:7]([F:11])[CH:6]=1)#[N:5]

Komponenten

7

Edukt 4

HCID 887Methanol2×HCID 5938132,4,5-TrifluorobenzonitrileHCID 23665647Potassium tert-butoxide3×HCID 66982760t-butyl 5-cyclopropyl-4-(2-hydroxyethyl)-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate

Produkt 1

HCID 71280857t-butyl 4-[2-(4-cyano-2-fluoro-5-methoxyphenoxy)ethyl]-5-cyclopropyl-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylateAusbeute 104,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-30 °C

Versuchsvorschrift

To a solution of 210 mg of 2,4,5-trifluorobenzonitrile and 500 mg of t-butyl 5-cyclopropyl-4-(2-hydroxyethyl)-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate in 15 ml of THF was added portionwise 150 mg of potassium t-butoxide, followed by stirring at −30° C. for 2 hours. Further, to the reaction mixture was added 0.15 ml of MeOH and then 150 mg of potassium t-butoxide was added portionwise thereto, followed by elevating the temperature to −10° C. and stirring for 15 hours. Further, to the reaction mixture were added 0.15 ml of MeOH, and then 150 mg of potassium t-butoxide was added portionwise thereto, followed by elevating the temperature to 0° C. and stirring for additional 14 hours. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous magnesium sulfate, and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: HEX-EtOAc)) to obtain 726 mg of t-butyl 4-[2-(4-cyano-2-fluoro-5-methoxyphenoxy)ethyl]-5-cyclopropyl-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate as a colorless viscous substance.

Aufarbeitung

  1. customto −10° C.
  2. stirringstirring for 15 hours
  3. customto 0° C.
  4. stirringstirring for additional 14 hours
  5. washwashed with water and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography (elution solvent: HEX-EtOAc))

Quellen und Nachweise

ORD-Eintrag
ord-f0e7665ac94f410da92775eeb880a1b3
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108977B2

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