Toluene → rac-(2'S,3'S,4'S)-6-chloro-2'-(3-chloro-2-fluoro-phenyl)-4'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-1'-carbonyl chloride

HRID 2065399Notes

Reaction equation

HRID 2065399 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:28])[C:10]3([CH:14]([CH2:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:13][NH:12][CH:11]3[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=3[F:27])[C:5]2=[CH:4][CH:3]=1.C([O-])(O)=O.[Na+].C1(C)C=CC=CC=1.[C:41](Cl)([Cl:43])=[O:42]>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:28])[C:10]3([CH:14]([CH2:15][C:16]([CH3:18])([CH3:19])[CH3:17])[CH2:13][N:12]([C:41]([Cl:43])=[O:42])[CH:11]3[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=3[F:27])[C:5]2=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 6371PhosgeneHCID 516892Sodium BicarbonateHCID 67336394rac-(2'S,3'S,4'S)-6-chloro-2'-(3-chloro-2-fluoro-phenyl)-4'-(2,2-dimethyl-propyl)-1H-spiro[indole-3,3'-pyrrolidin]-2-one

Product 1

HCID 76776161rac-(2'S,3'S,4'S)-6-chloro-2'-(3-chloro-2-fluoro-phenyl)-4'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-1'-carbonyl chloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(2,2-dimethyl-propyl)-1H-spiro[indole-3,3′-pyrrolidin]-2-one prepared in Example 6 (0.12 g, 0.28 mmol) in dichloromethane (3 mL) was added saturated aqueous NaHCO3 solution (3 mL). The temperature of the mixture was lowered to 0° C., and a toluene solution (Aldrich, 20%) of phosgene (0.27 mL, 0.51 mmol) was added dropwise via a syringe. The reaction mixture was stirred at room temperature for 30 min, then diluted dichloromethane. The organic layer was separated, the aqueous layer was extracted with dichlormethane twice. The combined organic layers were washed with water, brine, dried over MgSO4, and concentrated to give crude rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-1′-carbonyl chloride as a light yellow oil, which was used in the next step without further purification (0.14 g, 100%).

Workup

  1. customwas lowered to 0° C.
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with dichlormethane twice
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-5c138cf240d141249b19660a1d1a827b
Source dataset
uspto-grants-2012_10
Patent number
US08288431B2

Reaction notes

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