反応 #41850

反応方程式

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

収率 56.4%

溶媒

DCM

EtOAc

反応条件

後処理

1. 1
   温度to warm to r.t.
2. 2
   workup.STIRRINGagitated for 1.5 h
3. 3
   ろ過The reaction mixture was filtered
4. 4
   濃縮concentrated
5. 5
   workup.DISSOLUTIONThe resulting residue was dissolved in glacial acetic acid (60 mL)
6. 6
   温度heated to 100° C
7. 7
   温度the resulting mixture heated at 100° C. for 1 h
8. 8
   乾燥The organic layer was dried over sodium sulfate
9. 9
   濃縮concentrated
10. 10
    workup.ADDITIONThe residue was treated with diethyl ether
11. 11
    ろ過the resulting solid filtered
12. 12
    洗浄washed with diethyl ether

実験手順

(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 agitated 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).

出典