Phosgene → rac-(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl chloride

HRID 909057Notes

Reaction equation

HRID 909057 reaction equation
[Cl:1][C:2]1[C:3]([F:28])=[C:4]([CH:8]2[CH2:12][NH:11][CH:10]([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[C:9]2([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=2[F:27])[C:18]#[N:19])[CH:5]=[CH:6][CH:7]=1.C([O-])(O)=O.[Na+].[C:34](Cl)([Cl:36])=[O:35]>ClCCl>[Cl:1][C:2]1[C:3]([F:28])=[C:4]([CH:8]2[CH2:12][N:11]([C:34]([Cl:36])=[O:35])[CH:10]([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[C:9]2([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=2[F:27])[C:18]#[N:19])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6371PhosgeneHCID 516892Sodium BicarbonateHCID 67095302rac-(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-2-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile

Product 1

HCID 76707490rac-(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl chlorideYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of rac-(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-2-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile prepared in Example 3 (0.3 g, 0.71 mmol) in dichloromethane (5 mL) was added saturated aqueous NaHCO3 solution (5 mL). The temperature of the mixture was lowered to 0° C., and a solution of phosgene (Aldrich, 20% in toluene, 0.67 mL, 1.28 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 dichloromethane (2×). The combined organic layers were washed with water, brine, dried over MgSO4, and concentrated to give crude rac-(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl chloride as a light yellow oil (0.34 g, 100%).

Workup

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

Sources & evidence

ORD record
ord-b1b727548d9544da944d17659d93e4ac
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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