Water → (-)-(cis)-N-(7-cyano-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-2,2,2-trifluoroacetamide

HRID 1668360Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1668360
Br[C:2]1[C:28]([F:29])=[CH:27][C:5]2[O:6][C:7]3[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:8]=3[C@H:9]3[C@H:14]([NH:15][C:16](=[O:21])[C:17]([F:20])([F:19])[F:18])[CH2:13][CH2:12][CH2:11][N:10]3[C:4]=2[CH:3]=1.[C:30]([Cu])#[N:31].CN1C(=O)CCC1.O>C(OCC)(=O)C.[Cu]I>[C:30]([C:2]1[C:28]([F:29])=[CH:27][C:5]2[O:6][C:7]3[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:8]=3[C@H:9]3[C@H:14]([NH:15][C:16](=[O:21])[C:17]([F:20])([F:18])[F:19])[CH2:13][CH2:12][CH2:11][N:10]3[C:4]=2[CH:3]=1)#[N:31]

Komponenten

7

Edukt 4

HCID 962WaterHCID 13387N-methyl-2-pyrrolidoneHCID 86619616(-)-(cis)-N-(7-bromo-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-2,2,2-trifluoroacetamideHCID 178418546HCID 178418546, Verbindung

Produkt 1

HCID 86619617(-)-(cis)-N-(7-cyano-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-2,2,2-trifluoroacetamideAusbeute 59,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
180 °C

Versuchsvorschrift

A mixture of 2.74 g (5.74 mmol) of (−)-(cis)-N-(7-bromo-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-2,2,2-trifluoroacetamide, CuCN (1.3 g, 14.3 mmol), CuI (0.123 g, 0.57 mmol) and NMP (25 mL) was stirred in a microwave for 20 min. at 180° C., 300 Watt with cooling. After cooling down, the reaction mixture was poured into water (500 mL). The precipitate, containing product and salts, was redissolved in ethyl acetate and the salts were filtered off. The organic layer was washed with NH4OH-solution, water, and brine, dried, and concentrated to give the crude compound which was crystallized to give the title compound (1.45 g, 59%). 1H-NMR (400 MHz, DMSO) 1.60-1.86 (m, 3H), 2.01 (m, 1H), 3.15 (m, 1H), 3.86 (m, 1H), 4.133 (d, J=10.0, 1H), 4.35 (m, 1H), 7.00 (m, 1H), 7.03 (m, 1H), 7.44 (d, J=7.7, 1H), 7.6 (d, J=6.3, 1H), 9.23 (br-d, J=7.8, 1H). (m/z)=424 (M+H)+.

Aufarbeitung

  1. temperature300 Watt with cooling
  2. temperatureAfter cooling down
  3. additionThe precipitate, containing product and salts
  4. filtrationthe salts were filtered off
  5. washThe organic layer was washed with NH4OH-solution, water, and brine
  6. customdried
  7. concentrationconcentrated
  8. customto give the crude compound which
  9. customwas crystallized

Quellen und Nachweise

ORD-Eintrag
ord-2ee863f7a7354cff859c805986182d36
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US07989442B2

Notizen zur Reaktion

Wird geladen…