反应 #1178443

反应方程式

diethyl azodicarboxylate

tert-butyl (2R,4R)-4-hydroxy-2-(4-(3-oxomorpholin-4-yl)phenylcarbamoyl]pyrrolidine-1-carboxylate

p-nitrobenzoic acid

triphenylphosphine

→

tert-butyl-(2R,4S)-4-(4-nitrobenzoyloxy)-2-[4-(3-oxomorpholin-4-yl)phenylcarbamoyl]pyrrolidine-1-carboxylate

溶剂

tetrahydrofuran

反应条件

后处理

1. 1
   workup.WAITThe reaction mixture is subsequently left
2. 2
   其他evaporated to dryness-under reduced pressure, 20 ml of methylene chloride
3. 3
   workup.ADDITIONare added to the residue
4. 4
   洗涤the methylene chloride solution is washed successively with 10 ml of saturated sodium chloride solution and 10 ml of water
5. 5
   干燥dried over sodium sulfate
6. 6
   过滤After the drying agent has been filtered off
7. 7
   其他the solvent has been stripped off in a rotary evaporator
8. 8
   其他the residue is triturated with 30 ml of diethyl ether

实验过程

8.1 5.51 ml (35 mmol) of diethyl azodicarboxylate (DEAD) are added dropwise at 0° C. under nitrogen to a solution of 7.0 g (7.26 mmol) of tert-butyl (2R,4R)-4-hydroxy-2-(4-(3-oxomorpholin-4-yl)phenylcarbamoyl]pyrrolidine-1-carboxylate, 5.77 g (34.5 mmol) of p-nitrobenzoic acid and 9.18 g (35 mmol) of triphenylphosphine in 350 ml of tetrahydrofuran. The reaction mixture is subsequently left to stir at room temperature for 12 hours and evaporated to dryness-under reduced pressure, 20 ml of methylene chloride are added to the residue, and the methylene chloride solution is washed successively with 10 ml of saturated sodium chloride solution and 10 ml of water and dried over sodium sulfate. After the drying agent has been filtered off and the solvent has been stripped off in a rotary evaporator, the residue is triturated with 30 ml of diethyl ether, giving 8.5 g (88.8%) of tert-butyl-(2R,4S)-4-(4-nitrobenzoyloxy)-2-[4-(3-oxomorpholin-4-yl)phenylcarbamoyl]pyrrolidine-1-carboxylate as slightly yellow crystals, ESI 555. 8.2 Analogously to Example 7, reaction of tert-butyl (2R,4S)-4-(4-nitro-benzoyloxy)-2-[4-(3-oxomorpholin-4-yl)phenylcarbamoyl]pyrrolidine-1-carboxylate gives the compound (3S,5R)-1-(4-chlorophenylcarbamoyl)-5-[4-(3-oxomorpholin-4-yl)phenylcarbamoyl]pyrrolidin-3-yl 4-nitrobenzoate as yellowish crystals, ESI 608. 8.3 0.075 ml of 1N sodium hydroxide solution is added with ice cooling to the solution of 50 mg (0.082 mmol) of (3S,5R)-1-(4-chlorophenyl-carbamoyl)-5-[4-(3-oxomorpholin-4-yl)phenylcarbamoyl]pyrrolidin-3-yl 4-nitrobenzoate in 2 ml of methanol, and the reaction mixture is stirred for 15 minutes. The precipitate is filtered off and washed with 2 ml of methanol and dried, giving 35 mg (93%) of 1-N-[(4-chlorophenyl)]-2-N-{[4-(3-oxomorpholin-4-yl)phenyl]}-(2R,4S)-4-hydroxypyrrolidine-1,2-dicarboxamide as colourless crystals, ESI 459, m.p. 243° (decomposition).

来源