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Diphenylphosphinic chloride → HCID 53357877, compound

HRID 1807293
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Reaction equation

HRID 1807293 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.[CH3:56][O:57][C:58]([C:60]1[O:61][C:62]2[CH:68]=[CH:67][C:66]([NH2:69])=[CH:65][C:63]=2[N:64]=1)=[O:59]>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:69][C:66]2[CH:67]=[CH:68][C:62]3[O:61][C:60]([C:58]([O:57][CH3:56])=[O:59])=[N:64][C:63]=3[CH:65]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 73910Diphenylphosphinic chlorideHCID 81531DiisopropylethylamineHCID 18550976Methyl 5-aminobenzo[d]oxazole-2-carboxylateHCID 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 53357877HCID 53357877, 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 (59.8 mg, 0.128 mmol) in dichloromethane (3 ml) was treated with DIPEA (66.8 mg, 0.517 mmol) and DIPHENYLPHOSPHINIC CHLORIDE (80.7 mg, 0.341 mmol) and stirred for 20 min under argon. 5-AMINO-BENZOOXAZOLE-2-CARBOXYLIC ACID METHYL ESTER (25.8 mg, 134 μmol, JW PharmLab) was added and stirred 2 hrs. The reaction mixture was diluted with dichloromethane and washed with water, sat'd NaHCO3, water and brine. After drying over Na2SO4 the crude material was purified by silica gel chromatography with ethyl acetate and n-hexanes giving chiral methyl 5-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)benzo[d]oxazole-2-carboxylate (73.7 mg., 89.8%) as a white lyophilized solid. MS (ES+) m/z Calcd: [(M+H)+]: 641.15. found: 641.2.

Workup

  1. stirringstirred 2 hrs
  2. washwashed 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 5-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)benzo[d]oxazole-2-carboxylate (73.7 mg., 89.8%) as

Sources & evidence

ORD record
ord-63087a6124364997bf628bfda3117e38
Source dataset
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08354444B2

Reaction notes

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