Reaktion #66279

Reaktionsgleichung

(1E,4E)-8-bromo-2-(tert-butoxycarbonylamino)-3H-benzo[b]azepine-4-carboxylic acid

dipropylamine

EDCI

HOBt

diisopropylethylamine

→

tert-butyl (1E,4E)-8-bromo-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate

Ausbeute 76.3%

Lösungsmittel

CH2Cl2

ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturmaintaining the reaction temperature between −15 to −12° C
2. 2
   TemperaturThe resulting mixture was warmed to room temperature
3. 3
   workup.STIRRINGstirred for 19 h
4. 4
   workup.ADDITIONThe reaction mixture was poured onto water (50 mL)
5. 5
   SonstigeThe organic layer was separated
6. 6
   Extraktionthe aqueous layer was extracted with CH2Cl2 (50 mL)
7. 7
   WaschenThe combined organic layers were washed with sat'd aq NH4Cl (75 mL)
8. 8
   SonstigeThe organic layer was separated
9. 9
   ExtraktionThe sat'd aq NH4Cl solution was extracted with CH2Cl2 (50 mL) again
10. 10
    WaschenThe combined organic layers were washed with sat'd aq NaHCO3 (2×75 mL)
11. 11
    TrocknenThe organic layer was dried over MgSO4
12. 12
    Filtrationfiltered
13. 13
    Einengenconcentrated under reduced pressure
14. 14
    Sonstigeto give the crude material that
15. 15
    workup.WAITkept in the freezer for 16 h
16. 16
    FiltrationThe precipitates were filtered off
17. 17
    Einengenthe filtrate was concentrated under reduced pressure

Vorschrift

To a solution of dipropylamine (2.16 ml, 15.7 mmol) in CH2Cl2 (50 mL) at −10° C. was added EDCI (3.02 g, 15.7 mmol) followed by diisopropylethylamine (2.97 ml, 17.1 mmol) over 5 min. The resulting mixture was stirred for 40 min at −15° C. To the reaction mixture was added (1E,4E)-8-bromo-2-(tert-butoxycarbonylamino)-3H-benzo[b]azepine-4-carboxylic acid (5.00 g, 13.1 mmol) followed by HOBt (2.13 g, 15.7 mmol) over 5 min maintaining the reaction temperature between −15 to −12° C. The resulting mixture was warmed to room temperature and stirred for 19 h. The reaction mixture was poured onto water (50 mL). The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (50 mL). The combined organic layers were washed with sat'd aq NH4Cl (75 mL). The organic layer was separated. The sat'd aq NH4Cl solution was extracted with CH2Cl2 (50 mL) again. The combined organic layers were washed with sat'd aq NaHCO3 (2×75 mL) followed by brine (2×100 mL). The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was taken into ether (50 mL) and kept in the freezer for 16 h. The precipitates were filtered off and the filtrate was concentrated under reduced pressure to afford 4.64 g (76%) of tert-butyl (1E,4E)-8-bromo-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate. MS APCI(+) m/z 464, 466 (M+1, Br pattern) detected.

Quelle