Phosgene → HCID 51353870, compound
Reaction equation
[Cl:1][C:2]1[C:3]([F:28])=[C:4]([CH:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:10][NH:9]2)[CH:5]=[CH:6][CH:7]=1.[C:29](Cl)(Cl)=[O:30].C(N(CC)CC)C.[CH3:40][O:41][C:42](=[O:51])[C:43]1[CH:48]=[CH:47][C:46]([CH2:49][NH2:50])=[CH:45][CH:44]=1>C(Cl)Cl>[CH3:40][O:41][C:42](=[O:51])[C:43]1[CH:48]=[CH:47][C:46]([CH2:49][NH:50][C:29]([N:9]2[CH2:10][C@@H:11]([CH2:23][C:24]([CH3:25])([CH3:27])[CH3:26])[C@@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:8]2[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:28])=[O:30])=[CH:45][CH:44]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
In a manner similar to the method described in Example 4, rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (126.9 mg, 0.30 mmol) was reacted with phosgene solution (Aldrich, 20% in toluene, 0.45 mL, 0.45 mmol), in the presence of triethylamine (TEA, 272.7 mg, 2.7 mmol) in CH2Cl2 (10 mL) followed by reacting with 4-aminomethyl-benzoic acid methyl ester (90.7 mg, 0.45 mmol) at rt for 30 min to give rac-4-({[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]amino}-methyl)-benzoic acid methyl ester (108.0 mg, 59.9%) as a white amorphous which was used in the next step without further purification.
Sources & evidence
- ORD record
- ord-861f8aaa6a004a51a176bf8b51ce371f
- Source dataset
- uspto-grants-2011_09
- Patent number
- US08017607B2
Reaction notes
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