تفاعل #67335

معادلة التفاعل

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

المردود 56.4%

المذيبات

DCM

EtOAc

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةto warm to r.t.
2. 2
   workup.WAITagiated for 1.5 h
3. 3
   ترشيحThe reaction mixture was filtered
4. 4
   تركيزconcentrated
5. 5
   workup.DISSOLUTIONThe resulting residue was dissolved in glacial acetic acid (60 mL)
6. 6
   درجة الحرارةheated to 100° C
7. 7
   درجة الحرارةthe resulting mixture heated at 100° C. for 1 h
8. 8
   تجفيفThe organic layer was dried over sodium sulfate
9. 9
   تركيزconcentrated
10. 10
    workup.ADDITIONThe residue was treated with diethyl ether
11. 11
    ترشيحthe resulting solid filtered
12. 12
    غسيلwashed with diethyl ether

الإجراء التجريبي

(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).

المصدر