Ethyl Acetate → HCID 59594376, Verbindung

HRID 885008Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 885008
[Cl:1][C:2]1[CH:22]=[CH:21][C:5]2[N:6]([CH3:20])[C:7](=[O:19])[CH2:8][N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.CC(C)([O-])C.[K+].[Cl:29][C:30]1[CH:37]=[CH:36][CH:35]=[CH:34][C:31]=1[CH2:32]Br.C(OCC)(=O)C>C1COCC1>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]2[N:6]([CH3:20])[C:7](=[O:19])[CH:8]([CH2:32][C:31]3[CH:34]=[CH:35][CH:36]=[CH:37][C:30]=3[Cl:29])[N:9]=[C:10]([C:11]3[CH:12]=[CH:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=3)[C:4]=2[CH:3]=1

Komponenten

6

Edukt 4

HCID 8857Ethyl Acetate2×HCID 11905alpha-Bromo-o-chlorotoluene2×HCID 308581814-BENZDIAZPIN-2-ONE,1ME5-(4MEOPH)7CLHCID 23665647Potassium tert-butoxide

Produkt 1

HCID 59594376HCID 59594376, VerbindungAusbeute 83,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

(Z)-7-Chloro-5-(4-methoxyphenyl)-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one (0.2 g, 0.635 mmol) was dissolved in dry THF (5 mL) under nitrogen and cooled to −78° C. Potassium tert-butoxide (86 mg, 0.762 mmol) was added as a solid in two portions with rapid stirring. The mixture instantly colored and rapidly turned deep red. After 5 min, 2-chlorobenzyl bromide (107 μL, 0.836 mmol) was added dropwise by syringe. The mixture was allowed to stir at −78° C. for 1 h under nitrogen. It turned a light brown color. TLC (1:1 hexanes:ethyl acetate) indicated no starting material remained with a major less polar product and a minor more polar product plus some residual 2-chlorobenzylbromide. The reaction was quenched cold by adding ˜2 mL 1:1 methanol:water. A yellow precipitate formed. The cold bath was removed and the mixture was allowed to warm to room temperature. Water and ethyl acetate were added. The organic layer was separated and washed one time with brine then dried over magnesium sulfate, filtered and the solvent evaporated. Chromatography on a 10 g silica gel eluting with a gradient of 30-50% ethyl acetate in hexanes gave (Z)-7-chloro-3-(2-chlorobenzyl)-5-(4-methoxyphenyl)-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one as a yellow oil (232 mg, 0.528 mmol, 83%). 1H NMR (300 MHz, CDCl3) δ 3.37 (s, 3H), 3.6-3.75 (m, 2H), 3.79-3.86 (m, 1H), 3.81 (s, 3H), 6.85 (d, J=9 Hz, 2H), 7.1-7.6 (m, 9H); ESI m/z 439.6 [M+H+].

Aufarbeitung

  1. customThe reaction was quenched cold
  2. additionby adding ˜2 mL 1:1 methanol
  3. customA yellow precipitate formed
  4. customThe cold bath was removed
  5. temperatureto warm to room temperature
  6. additionWater and ethyl acetate were added
  7. customThe organic layer was separated
  8. washwashed one time with brine
  9. dry with materialthen dried over magnesium sulfate
  10. filtrationfiltered
  11. customthe solvent evaporated

Quellen und Nachweise

ORD-Eintrag
ord-1890959c255145beac003036e053c4f9
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08242109B2

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