Diphenylphosphinic chloride → HCID 53357875, compound

HRID 1807291Notes

Reaction equation

HRID 1807291 reaction equation
[Cl:1][C:2]1[C:3]([F:31])=[C:4]([C@@H: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])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28](O)=[O:29])[CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[NH2:56][C:57]1[CH:62]=[CH:61][C:60]([CH2:63][CH2:64][CH2:65][C:66]([O:68][CH3:69])=[O:67])=[CH:59][CH:58]=1>ClCCl>[Cl:1][C:2]1[C:3]([F:31])=[C:4]([C@@H: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])[C@H:11]([CH2:23][C:24]([CH3:26])([CH3:27])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:56][C:57]2[CH:58]=[CH:59][C:60]([CH2:63][CH2:64][CH2:65][C:66]([O:68][CH3:69])=[O:67])=[CH:61][CH:62]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 73910Diphenylphosphinic chlorideHCID 81531DiisopropylethylamineHCID 88628Methyl 4-aminobenzenebutanoateHCID 59249226(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxylic acid

Product 1

HCID 53357875HCID 53357875, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of chiral (2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (60.9 mg, 0.130 mmol) in dichloromethane (3 ml) were added DIPEA (66.8 mg, 0.514 mmol) and DIPHENYLPHOSPHINIC CHLORIDE (78.2 mg, 0.324 mmol). The mixture was stirred for 20 mins under argon before methyl 4-(4-aminophenyl)butanoate (24.7 mg, 0.128 mmol) was added. After 2 hrs, the reaction mixture was diluted with dichloromethane and extracted with water then with sat. NaHCO3, water, and sat. NaCl. After drying over Na2SO4 the crude material was purified by silica gel chromatography with ethyl acetate and n-hexanes giving chiral methyl 4-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)phenyl)butanoate (79.2 mg., 96%) as a white solid. MS (ES+) m/z Calcd: [(M+H)+]: 642.2. found: 642.1.

Workup

  1. additionwas added
  2. extractionextracted with water
  3. dry with materialAfter drying over Na2SO4 the crude material
  4. customwas purified by silica gel chromatography with ethyl acetate and n-hexanes giving chiral methyl 4-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)phenyl)butanoate (79.2 mg., 96%) as a white solid

Sources & evidence

ORD record
ord-31c05de2fdfa4c1a9bf38aa6b9e02f37
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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