Sodium Carbonate → (S)-2-tert-Butoxycarbonylamino-3-{(S)-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl}-propionic acid methyl ester

Temperatur

-20 °C

(S)-2-tert-Butoxycarbonylamino-3-(4-hydroxy-3-nitro-phenyl)-propionic acid methyl ester (16.8 mmol) and (R)-[4-(3,4-dichloro-benzyloxy)-phenyl]-hydroxy-acetic acid methyl ester (20.1 mmol) were dissolved in 80 mL of DCM, resin-bound triphenylphosphine (33.6 mmol) added and the mixture cooled to −20° C. To this solution was added DIAD (25.2 mmol) and the mixture was agitated for 30 min at −20° C. The mixture was slowly allowed to warm to r.t. and agiated for 1.5 h. The reaction mixture was filtered and concentrated. The resulting residue was dissolved in glacial acetic acid (60 mL) and heated to 100° C. Iron powder (336 mmol) was added and the resulting mixture heated at 100° C. for 1 h. The mixture was poured onto water and EtOAc. The mixture was brought to ˜pH 7 with sodium carbonate. The organic layer was dried over sodium sulfate and concentrated. The residue was treated with diethyl ether and the resulting solid filtered and washed with diethyl ether to provide (S)-2-tert-Butoxycarbonylamino-3-{(S)-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl}-propionic acid methyl ester (5.7 g). LC-MS (m/z) 502 (M-Boc).

1. temperatureto warm to r.t.
2. waitagiated for 1.5 h
3. filtrationThe reaction mixture was filtered
4. concentrationconcentrated
5. dissolutionThe resulting residue was dissolved in glacial acetic acid (60 mL)
6. temperatureheated to 100° C
7. temperaturethe resulting mixture heated at 100° C. for 1 h
8. dry with materialThe organic layer was dried over sodium sulfate
9. concentrationconcentrated
10. additionThe residue was treated with diethyl ether
11. filtrationthe resulting solid filtered
12. washwashed with diethyl ether

ORD-Eintrag

ord-7793a4f10ee14ae2b1fa2621295ffeec

Quelldatensatz

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07906507B2