Réaction #67335

Équation de réaction

DIAD

(S)-2-tert-Butoxycarbonylamino-3-(4-hydroxy-3-nitro-phenyl)-propionic acid methyl ester

(R)-[4-(3,4-dichloro-benzyloxy)-phenyl]-hydroxy-acetic acid methyl ester

sodium carbonate

triphenylphosphine

→

(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

Rendement 56.4%

Solvants

DCM

EtOAc

Conditions de réaction

Traitement

1. 1
   Températureto warm to r.t.
2. 2
   workup.WAITagiated for 1.5 h
3. 3
   FiltrationThe reaction mixture was filtered
4. 4
   Concentrationconcentrated
5. 5
   workup.DISSOLUTIONThe resulting residue was dissolved in glacial acetic acid (60 mL)
6. 6
   Températureheated to 100° C
7. 7
   Températurethe resulting mixture heated at 100° C. for 1 h
8. 8
   SéchageThe organic layer was dried over sodium sulfate
9. 9
   Concentrationconcentrated
10. 10
    workup.ADDITIONThe residue was treated with diethyl ether
11. 11
    Filtrationthe resulting solid filtered
12. 12
    Lavagewashed with diethyl ether

Mode opératoire

(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).

Source