تفاعل #1449240

معادلة التفاعل

P(o-tol)3

(7-Bromo-2-oxo-1,2,3,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-4-yl)acetic acid ethyl ester

tert-butyl acrylate

(i-Pr)2EtN

→

title compound

المردود 39.0%

(E)-3-(4-Ethoxycarbonylmethyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid tert-butyl ester

المردود 39.0%

المذيبات

propionitrile

DMF

ظروف التفاعل

المعالجة

1. 1
   workup.WAITde-oxygenated with Ar for 10 min
2. 2
   أخرىfor 5 min
3. 3
   درجة الحرارةAfter heating
4. 4
   درجة الحرارةto reflux for 14 h
5. 5
   درجة الحرارةto cool
6. 6
   تركيزconcentrated in vacuo
7. 7
   workup.ADDITIONThe resulting residue was diluted with CH2Cl2
8. 8
   ترشيحfiltered through Celite
9. 9
   تركيزThe orange filtrate was concentrated in vacuo
10. 10
    workup.ADDITIONThe resulting residue was diluted with EtOAc (200 mL)
11. 11
    غسيلwashed with H2O (100 mL)
12. 12
    استخلاصThe aqueous layer was extracted with EtOAc (2×100 mL)
13. 13
    غسيلThe combined organic layers were washed with H2O (2×100 mL) and brine (100 mL)
14. 14
    تجفيفdried over Na2SO4
15. 15
    ترشيحfiltered
16. 16
    أخرىthe solvent was removed in vacuo
17. 17
    أخرىPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3)

الإجراء التجريبي

A suspension of (7-Bromo-2-oxo-1,2,3,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-4-yl)acetic acid ethyl ester (6.18 g, 17.4 mmol) in propionitrile (70 mL) and DMF (17 mL) was de-oxygenated with Ar for 30 min. The mixture was treated with tert-butyl acrylate (10.2 mL, 69.6 mmol) and (i-Pr)2EtN (6.4 mL, 37 mmol) and was then de-oxygenated with Ar for 10 min. Pd(OAc)2 (0.39 g, 1.7 mmol) and P(o-tol)3 (1.06 mg, 3.48 mmol) were added simultaneously, and the mixture was de-oxygenated a third time for 5 min. After heating to reflux for 14 h, the mixture was allowed to cool and then concentrated in vacuo. The resulting residue was diluted with CH2Cl2 and filtered through Celite. The orange filtrate was concentrated in vacuo. The resulting residue was diluted with EtOAc (200 mL) and washed with H2O (100 mL). The aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with H2O (2×100 mL) and brine (100 mL), dried over Na2SO4, filtered and the solvent was removed in vacuo. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3) and again by flash column chromatography (silica gel, CH2Cl2/MeOH, 99:1) gave the title compound (2.55 g, 39%) as an off-white solid: MS (ESI) m/e 376 (M+H)+.

المصدر