Reaction #710522

Reaction equation

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

Yield 89.5%

Solvents

methanol

methanol

Conditions

Workup

1. 1
   Otherwas evaporated under reduced pressure
2. 2
   ExtractionThe remaining aqueous phase was extracted 3 times with 20 mL of dichloromethane
3. 3
   WashThe combined organic extracts were washed with 20 mL of brine
4. 4
   Dryingdried with magnesium sulfate
5. 5
   Concentrationconcentrated to dryness under reduced pressure

Procedure

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).

Source