반응 #710521

반응 방정식

water

ethyl acetate

(2′S,3′R,4′S,5′R)-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

acetyl chloride

pyridine

→

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

반응 조건

후처리

1. 1
   기타The organic phase was separated
2. 2
   추출the aqueous phase was extracted twice with ethyl acetate
3. 3
   세척The combined organic extracts were washed with brine
4. 4
   건조dried with magnesium sulfate
5. 5
   농축concentrated to dryness under reduced pressure
6. 6
   기타The residue was purified by flash chromatography on a 50 g silica cartridge (15-40 μm silica gel; eluting solvent: dichloromethane/methanol 98/2 v/v; flow: 40 mL/min)
7. 7
   기타followed by a second purification by flash chromatography on a 30 g silica cartridge (15-40 μm silica gel; eluting solvent: dichloromethane/methanol 98/2 v/v; flow: 20 mL/min) 123 mg of acetic acid 4-{[(2′S,3R,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′-pyrrolidin]e-5′-carbonyl]-amino}-cyclohexyl ester
8. 8
   기타were obtained as a white powder

실험 절차

To a solution of 281 mg (0.50 mmol) of (2′S,3′R,4′S,5′R)-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 in 5.0 mL of pyridine under argon, was added 178 μL (2.50 mmol) of acetyl chloride. The resulting mixture was stirred at room temperature for 4 days, upon which it was poured into a mixture of water and ethyl acetate. The organic phase was separated and the aqueous phase was extracted twice with ethyl acetate. The combined organic extracts were washed with brine, dried with magnesium sulfate and then concentrated to dryness under reduced pressure. The residue was purified by flash chromatography on a 50 g silica cartridge (15-40 μm silica gel; eluting solvent: dichloromethane/methanol 98/2 v/v; flow: 40 mL/min) followed by a second purification by flash chromatography on a 30 g silica cartridge (15-40 μm silica gel; eluting solvent: dichloromethane/methanol 98/2 v/v; flow: 20 mL/min) 123 mg of acetic acid 4-{[(2′S,3R,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′-pyrrolidin]e-5′-carbonyl]-amino}-cyclohexyl ester were obtained as a white powder. LC-MS: tR (min)=1.19; [M+H]+: m/z 688; [M−H]−: m/z 686 (method A).

출처