반응 #66279

반응 방정식

(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

수율 76.3%

용매

CH2Cl2

ether

반응 조건

후처리

1. 1
   온도maintaining the reaction temperature between −15 to −12° C
2. 2
   온도The 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
   기타The organic layer was separated
6. 6
   추출the aqueous layer was extracted with CH2Cl2 (50 mL)
7. 7
   세척The combined organic layers were washed with sat'd aq NH4Cl (75 mL)
8. 8
   기타The organic layer was separated
9. 9
   추출The sat'd aq NH4Cl solution was extracted with CH2Cl2 (50 mL) again
10. 10
    세척The combined organic layers were washed with sat'd aq NaHCO3 (2×75 mL)
11. 11
    건조The organic layer was dried over MgSO4
12. 12
    여과filtered
13. 13
    농축concentrated under reduced pressure
14. 14
    기타to give the crude material that
15. 15
    workup.WAITkept in the freezer for 16 h
16. 16
    여과The precipitates were filtered off
17. 17
    농축the filtrate was concentrated under reduced pressure

실험 절차

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.

출처