Methanol → 2-(difluoromethoxy)-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine

HRID 597927Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 597927
[F:1][CH:2]([F:22])[O:3][C:4]1[CH:5]=[CH:6][C:7]2[CH:13]([CH3:14])[CH2:12][N:11](C(=O)C(F)(F)F)[CH2:10][CH2:9][C:8]=2[N:21]=1.C([O-])([O-])=O.[K+].[K+].CO>O>[F:22][CH:2]([F:1])[O:3][C:4]1[CH:5]=[CH:6][C:7]2[CH:13]([CH3:14])[CH2:12][NH:11][CH2:10][CH2:9][C:8]=2[N:21]=1

Komponenten

5

Edukt 3

HCID 887MethanolHCID 11430Potassium CarbonateHCID 86616698HCID 86616698, Verbindung

Produkt 1

HCID 236539042-(difluoromethoxy)-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepineAusbeute 36 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

To a mixture of 5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-2-ol (77.0 mg, 281 μmol), K2CO3 (19.0 mg, 141 μmol) and DMF (1.4 ml) was added F2ClCCO2Na (47.0 mg, 310 μmol). The mixture was heated at 90° C. for 2 h. The reaction mixture was parted between sat. aq. NaHCO3 and EtOAc. The organic layer was dried, concentrated in vacuo and purified by means of column chromatography to give 49.0 mg (54%) of 2-(difluoromethoxy)-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. MS (ESI) m/z 325.2. A mixture of 2-(difluoromethoxy)-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (28.0 mg, 86.0 μmol), K2CO3 (30 mg), MeOH (1 ml) and H2O (200 μl) was heated to reflux for 10 min. The reaction mixture was concentrated in vacuo and the resulting residue was purified by column chromatography to yield 7.0 mg (36%) of 2-(difluoromethoxy)-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 7.46 (d, 1H), 6.66 (d, 1H), 3.09 (m, 2H), 3.40-2.90 (m, 4H), 2.74, (dd, 1H), 1.31 (d, 3H) ppm.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureto reflux for 10 min
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthe resulting residue was purified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-009c42a338a143a2b508dcc63afe4d21
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07897595B2

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