Sodium Hydroxide → rac-(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

HRID 417379Notes

Reaction equation

HRID 417379 reaction equation
COC(=O)C1C=CC(N[C:11]([C@@H:13]2[NH:17][C@@H:16]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C@:15]3([C:30]4[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=4)[NH:24][C:23]3=[O:32])[C@H:14]2[C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[C:34]=2[F:40])=[O:12])=CC=1Cl.[OH-:43].[Na+]>CO.O1CCCC1>[Cl:31][C:27]1[CH:26]=[C:25]2[NH:24][C:23](=[O:32])[C:15]3([CH:14]([C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[C:34]=4[F:40])[CH:13]([C:11]([OH:43])=[O:12])[NH:17][CH:16]3[CH2:18][C:19]([CH3:20])([CH3:22])[CH3:21])[C:30]2=[CH:29][CH:28]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 53237290HCID 53237290, compound

Product 1

HCID 66625245rac-(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 acidYield 66%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a manner similar to the methods described in Example 16 and Example 22, rac-2-chloro-4-{[(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′-carbonyl]-amino}-benzoic acid methyl ester prepared in Example 24 (78 mg, 0.12 mmol) was hydrolyzed with aqueous NaOH in methanol and tetrahydrofuran at 78° C. to give rac-(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 (50 mg, 66%), then rac-(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 (30 mg, 0.049 mmol) was reacted with EDCI (19 mg, 0.097 mmol), HOBt (13 mg, 0.097 mmol), triethyamine (9.8 mg, 0.097 mmol), and NH4Cl (26 mg, 0.49 mmol) at 80° C. to give rac-(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 (4-carbamoyl-3-chloro-phenyl)-amide as a off white solid (Yield, 35 mg, 64%).

Sources & evidence

ORD record
ord-a2486d6cc9bd496c90bc0691dff873d6
Source dataset
uspto-grants-2012_01
Patent number
US08088815B2

Reaction notes

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