Pyridine → rac-(2'S,3'R,4'S,5'R)-2'-(3-acetoxy-2,2-dimethyl-propyl)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid tert-butyl ester

HRID 417257Notes

Reaction equation

HRID 417257 reaction equation
[C:1]([O:5][C:6]([CH:8]1[NH:12][CH:11]([CH2:13][C:14]([CH3:18])([CH3:17])[CH2:15][OH:16])[C:10]2([C:26]3[C:21](=[CH:22][C:23]([Cl:27])=[CH:24][CH:25]=3)[NH:20][C:19]2=[O:28])[CH:9]1[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[C:30]=1[F:36])=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.[C:43](Cl)(=[O:45])[CH3:44]>O1CCCC1>[C:1]([O:5][C:6]([CH:8]1[NH:12][CH:11]([CH2:13][C:14]([CH3:18])([CH3:17])[CH2:15][O:16][C:43](=[O:45])[CH3:44])[C:10]2([C:26]3[C:21](=[CH:22][C:23]([Cl:27])=[CH:24][CH:25]=3)[NH:20][C:19]2=[O:28])[CH:9]1[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[C:30]=1[F:36])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 66625192rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(3-hydroxy-2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid tert-butyl ester

Product 1

HCID 66625386rac-(2'S,3'R,4'S,5'R)-2'-(3-acetoxy-2,2-dimethyl-propyl)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid tert-butyl esterYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(3-hydroxy-2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid tert-butyl ester (0.3 g, 0.56 mmol) in tetrahydrofuran (2 mL) at 0° C. was added pyridine (44 mg, 0.56 mmol) and acetyl chloride (44 mg, 0.56 mmol). The mixture was stirred at room temperature for 1 h. The mixture was concentrated, and the residue was partitioned between ethyl acetate and water. The organic layer was separated, washed with water, saturated aqueous CuSO4, brine, dried over MgSO4, and concentrated to give as rac-(2′S,3′R,4′S,5′R)-2′-(3-acetoxy-2,2-dimethyl-propyl)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid tert-butyl ester as a yellow oil (0.24 g, 74%)

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with water, saturated aqueous CuSO4, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-921632b6ee3243468daff0109ab430ba
Source dataset
uspto-grants-2012_01
Patent number
US08088815B2

Reaction notes

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