Reaction #66280

Reaction equation

N2

Na2CO3

4,4′-(phenylphosphinidene)bisbenzenesulfonic acid dipotassium hydrate

4-(dimethylcarbamoyl)phenylboronic acid

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

→

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

Yield 83.5%

Solvents

water

EtOH

EtOAc

water

EtOH

Conditions

Workup

1. 1
   Otherwas bubbled with N2 for 10 min
2. 2
   OtherThe resulting mixture was bubbled with N2 for 10 min
3. 3
   TemperatureThe reaction mixture was cooled to room temperature
4. 4
   Concentrationconcentrated under reduced pressure
5. 5
   Otherto give the crude material that
6. 6
   FiltrationThe mixture was filtered through GF/F
7. 7
   Filtrationfilter
8. 8
   OtherThe aqueous layer was separated
9. 9
   Extractionextracted with EtOAc (10 mL)
10. 10
    WashThe combined organic layers were washed with brine (10 mL)
11. 11
    Dryingdried over MgSO4
12. 12
    Filtrationfiltered
13. 13
    Concentrationconcentrated under reduced pressure
14. 14
    Otherto give the crude product that
15. 15
    Otherwas purified by silica gel flash column chromatography (CH2Cl2 to 2% MeOH in CH2Cl2)

Procedure

To Na2CO3 (129 mg, 1.214 mmol) in a 50 mL round-bottom flask was added water (3.7 mL) was bubbled with N2 for 10 min. To this mixture was added tert-butyl (1E,4E)-8-bromo-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate (200 mg, 0.40 mmol) in EtOH (4.9 mL) at room temperature. The resulting mixture was bubbled with N2 for 10 min. Pd(OAc)2 (9.3 mg, 0.040 mmol) and 4,4′-(phenylphosphinidene)bisbenzenesulfonic acid dipotassium hydrate (45 mg, 0.081 mmol) were added. The resulting mixture was warmed to 65° C. with N2 bubbling. To this mixture was added a solution of 4-(dimethylcarbamoyl)phenylboronic acid (97 mg, 0.49 mmol) in EtOH (0.6 mL). The resulting mixture was stirred at 65° C. for 1 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to give the crude material that was diluted with water (5 mL) and EtOAc (10 mL). The mixture was filtered through GF/F filter. The aqueous layer was separated and extracted with EtOAc (10 mL). The combined organic layers were washed with brine (10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude product that was purified by silica gel flash column chromatography (CH2Cl2 to 2% MeOH in CH2Cl2) to afford 178 mg (83%) of tert-butyl (1E,4E)-8-(4-(dimethylcarbamoyl)phenyl)-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate. MS APCI(+) m/z 533 (M+1) detected.

Source