Phosgene → HCID 67095317, compound

HRID 909020Notes

Reaction equation

HRID 909020 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.[C:40]([O:44][C:45]([N:47]1[CH2:52][CH2:51][CH:50]([CH2:53][NH2:54])[CH2:49][CH2:48]1)=[O:46])([CH3:43])([CH3:42])[CH3:41]>C(Cl)Cl>[C:40]([O:44][C:45]([N:47]1[CH2:52][CH2:51][CH:50]([CH2:53][NH:54][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])[CH2:49][CH2:48]1)=[O:46])([CH3:43])([CH3:42])[CH3:41]

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 8471TriethylamineHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 67095372rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile

Product 1

HCID 67095317HCID 67095317, compoundYield 73.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 (42.3 mg, 0.10 mmol) was reacted with phosgene solution (Aldrich, 20% in toluene, 0.12 mL, 0.12 mmol), in the presence of triethylamine (TEA, 30.0 mg, 0.30 mmol) in CH2Cl2 (2 mL) followed by reacting with 4-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (66.3 mg, 0.30 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)-piperidine-1-carboxylic acid tert-butyl ester (48.5 mg, 73.0%) as a white amorphous.

Sources & evidence

ORD record
ord-b2db0c2a105940f5b5aa20c8fafd027a
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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