反応 #78244

ord-d14ea5484a5d4a679a7be8a97b8d4144

反応方程式

COC(=O)[C@@H]1C[C@@H](O)CN1C(=O)OC(C)(C)C
trans-1-(Boc)-4-hydroxy-L-proline methyl ester
Oc1ccc(Br)cc1
4-bromophenol
c1ccc(P(c2ccccc2)c2ccccc2)cc1
Ph3P
CCOC(=O)/N=N/C(=O)OCC
DEAD
COC(=O)[C@@H]1C[C@H](Oc2ccc(Br)cc2)CN1C(=O)OC(C)(C)C
cis-1-(Boc)-4-(4-bromo-phenoxy)-L-proline methyl ester
収率 67.5%

溶媒

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    その他The solvent was removed in vacuo
  2. 2
    その他The solids were removed by filtration
  3. 3
    その他the solvent evaporated under reduced pressure

実験手順

To a solution of trans-1-(Boc)-4-hydroxy-L-proline methyl ester (0.5 g) (2 mmol), 4-bromophenol (0.52 g) (1.5 eq.) and Ph3P (0.78 g) (1.5 eq.) in 10 mL of dry THF at 0° C. was added DEAD (0.47 mL) in a minimal volume of THF. The reaction mixture was warmed to RT overnight. The solvent was removed in vacuo and the resulting residue suspended in ether. The solids were removed by filtration and the solvent evaporated under reduced pressure to afford after SiO2 chromatography (eluent: cyclohexane/EtOAc-9/1), cis-1-(Boc)-4-(4-bromo-phenoxy)-L-proline methyl ester as a colorless oil (0.54 g). NMR (CDCl3, 200 MHz): 7.37 (2H, d), 6.70 (2H, d), 4.85 (1H, m), 4.37-4.6 (1H, m), 3.6-3.85 (5H, m), 2.35-2.50 (2H, m), 1.4-1.5(9H). To a solution cis-1-(Boc)-4-(4-bromo-phenoxy)-L-proline methyl ester (0.54 g) in 8 mL of DCM at 0° C. was added 2.5 mL of TFA. The reaction mixture was stirred at 0° C. for 1 h and warmed to RT for an additional hour. The solvents were evaporated in vacuo. The resulting residue was dissolved in water and the aqueous layer basified with aqueous NaHCO3 and extracted with EtOAc. The combined organic extracts were washed with water, dried over MgSO4, and the solvent was evaporated under reduced pressure to afford the titled compound as a colorless oil which solidified upon standing (0.39 g). NMR (CDCl3, 200 MHz): 7.35 (2H, d), 6.70 (2H, d), 4.8 (1H, m), 3.92 (1H, dd), 3.72 (3H, s), 3.35 (1H, d), 3.1 (1H, dd) 2.25-2.55 (2H, m).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US06710064B2uspto-grants-2004_03