반응 #67335

반응 방정식

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

수율 56.4%

용매

DCM

EtOAc

반응 조건

후처리

1. 1
   온도to warm to r.t.
2. 2
   workup.WAITagiated for 1.5 h
3. 3
   여과The reaction mixture was filtered
4. 4
   농축concentrated
5. 5
   workup.DISSOLUTIONThe resulting residue was dissolved in glacial acetic acid (60 mL)
6. 6
   온도heated to 100° C
7. 7
   온도the resulting mixture heated at 100° C. for 1 h
8. 8
   건조The organic layer was dried over sodium sulfate
9. 9
   농축concentrated
10. 10
    workup.ADDITIONThe residue was treated with diethyl ether
11. 11
    여과the resulting solid filtered
12. 12
    세척washed with diethyl ether

실험 절차

(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).

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