Potassium Carbonate → HCID 178473938, compound

HRID 1192025Notes

Reaction equation

HRID 1192025 reaction equation
C([N:4]1[C:45]2[C:40](=[CH:41][CH:42]=[C:43]([Cl:46])[CH:44]=2)[C@@:6]2([C@@H:10]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[C:12]=3[F:18])[C@H:9]([C:19]([NH:21][CH:22]3[CH2:27][CH2:26][CH:25]([O:28]C(=O)C)[CH2:24][CH2:23]3)=[O:20])[N:8]([C:32](=[O:34])[CH3:33])[C@H:7]2[CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C:5]1=[O:47])(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO>[OH:28][C@H:25]1[CH2:24][CH2:23][C@H:22]([NH:21][C:19]([C@@H:9]2[N:8]([C:32](=[O:34])[CH3:33])[C@@H:7]([CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C@:6]3([C:40]4[C:45](=[CH:44][C:43]([Cl:46])=[CH:42][CH:41]=4)[NH:4][C:5]3=[O:47])[C@H:10]2[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[C:12]=2[F:18])=[O:20])[CH2:27][CH2:26]1

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 68750302HCID 68750302, compound

Product 1

HCID 178473938HCID 178473938, compoundYield 89.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

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, 14 H); 3.51 (m, 1 H); 3.65 (m, 1 H); 4.28 (m broad, 1 H); 4.48 (dd, J=3.4 and 5.9 Hz, 1 H); 4.98 (d, J=10.3 Hz, 1 H); 6.65 (d, J=1.5 Hz, 1 H); 6.99 (t, J=7.8 Hz, 1 H); 7.05 to 7.48 (m, 5 H).

Workup

  1. customwas evaporated under reduced pressure
  2. extractionThe remaining aqueous phase was extracted 3 times with 20 mL of dichloromethane
  3. washThe combined organic extracts were washed with 20 mL of brine
  4. dry with materialdried with magnesium sulfate
  5. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-03730f5ecad641dc99fb67a5123797f8
Source dataset
uspto-grants-2014_03
Patent number
US08680132B2

Reaction notes

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