反应 #710522

反应方程式

acetic acid 4-{[(2′S,3′R,4′S,5′R)-1,1′-diacetyl-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carbonyl]-amino}-cyclohexyl ester

potassium carbonate

→

(2′S,3′R,4′S,5′R)-1′-acetyl-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (trans-4-hydroxy-cyclohexyl)-amide

收率 89.5%

溶剂

methanol

methanol

反应条件

后处理

1. 1
   其他was evaporated under reduced pressure
2. 2
   萃取The remaining aqueous phase was extracted 3 times with 20 mL of dichloromethane
3. 3
   洗涤The combined organic extracts were washed with 20 mL of brine
4. 4
   干燥dried with magnesium sulfate
5. 5
   浓缩concentrated to dryness under reduced pressure

实验过程

To a solution of 117 mg (0.17 mmol) of acetic acid 4-{[(2′S,3′R,4′S,5′R)-1,1′-diacetyl-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carbonyl]-amino}-cyclohexyl ester in 10.0 mL of methanol under argon, was added 10 mL (81 mmol) of a saturated potassium carbonate solution. The resulting mixture was stirred at room temperature for 1 hour, upon which the methanol was evaporated under reduced pressure. The remaining aqueous phase was extracted 3 times with 20 mL of dichloromethane. The combined organic extracts were washed with 20 mL of brine, dried with magnesium sulfate and then concentrated to dryness under reduced pressure. 92 mg of (2′S,3′R,4′S,5′R)-1′-acetyl-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (trans-4-hydroxy-cyclohexyl)-amide were obtained as a white powder. mp: 220° C. (Kofler); LC-MS: tR (min)=0.97; [M+H]+: m/z 604; [M−H]−: m/z 602 (method A); 1H NMR (60° C., CHLOROFORM-d, 400 MHz): 0.68 (s, 9H); 0.75 to 2.62 (m partially hidden, 14H); 3.51 (m, 1H); 3.65 (m, 1H); 4.28 (m broad, 1H); 4.48 (dd, J=3.4 and 5.9 Hz, 1H); 4.98 (d, J=10.3 Hz, 1H); 6.65 (d, J=1.5 Hz, 1H); 6.99 (t, J=7.8 Hz, 1H); 7.05 to 7.48 (m, 5H).

来源