Bromobenzene → 3-[2-(4-Phenoxy-phenyl)-morpholin-4-yl]-propionic acid tert-butyl ester

Temperature

140 °C

To a mixture of Cs2CO3 (70 mg; 0.21 mmol), 3-[2-(4-Hydroxy-phenyl)-morpholin-4-yl]-propionic acid tert-butyl ester (33.8 mg, 0.11 mmol) and bromobenzene (12.6 μL, 0.12 mmol) was added 0.5 mL of a freshly prepared catalyst stock solution (see below) in a 2-5 mL Biotage® microwave vial. The vial was briefly flushed with N2 and sealed to maintain a semi-inert atmosphere. The resulting mixture was heated for 22 h, at 140° C. After cooling to room temperature, water (5 mL) was added and the mixture was extracted with EtOAc (1×7.5 mL, 2×5 mL). The combined organic layers were concentrated in vacuo, and the residue was purified by preparative TLC (SiO2, CH2Cl2/MeOH 99:1) to afford 3-[2-(4-phenoxy-phenyl)-morpholin-4-yl]-propionic acid tert-butyl ester (49 mg). The catalyst stock solution was prepared as follows: To a suspension of copper(I)iodide (73 mg, 0.16 mmol) in anhydrous toluene (9 mL) was added 1-butylimidazole (127 μL; 120 mg; 0.41 mmol). The solution was purged with N2 for 15 min. and vigorously agitated until all the CuI had fully dissolved.

1. additionwas added 0.5 mL of a freshly prepared catalyst stock solution (see below) in a 2-5 mL Biotage® microwave vial
2. customThe vial was briefly flushed with N2
3. customsealed
4. temperatureto maintain a semi-inert atmosphere
5. temperatureAfter cooling to room temperature
6. additionwater (5 mL) was added
7. extractionthe mixture was extracted with EtOAc (1×7.5 mL, 2×5 mL)
8. concentrationThe combined organic layers were concentrated in vacuo
9. customthe residue was purified by preparative TLC (SiO2, CH2Cl2/MeOH 99:1)

ORD record

ord-5a05f5908df94d069b27f0a100857d0f

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09029371B2