Triphenylphosphine → (R)-4-((R)-1-(7-phenylquinolin-5-yloxy)ethyl)pyrrolidin-2-one

HRID 1496863Notes

Reaction equation

HRID 1496863 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([OH:17])[C:10]3[CH:11]=[CH:12][CH:13]=[N:14][C:15]=3[CH:16]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O[C@H:19]([C@H:21]1[CH2:25][N:24]([C@@H](C2C=CC=CC=2)C)[C:23](=[O:34])[CH2:22]1)[CH3:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(N=NC(OC(C)(C)C)=O)=O)(C)(C)C>C(Cl)Cl>[C:1]1([C:7]2[CH:16]=[C:15]3[C:10]([CH:11]=[CH:12][CH:13]=[N:14]3)=[C:9]([O:17][C@@H:19]([C@H:21]3[CH2:25][NH:24][C:23](=[O:34])[CH2:22]3)[CH3:20])[CH:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 58072048(R)-4-((S)-1-hydroxyethyl)-1-((R)-1-phenylethyl)pyrrolidin-2-oneHCID 1364132507-Phenylquinolin-5-ol

Product 1

HCID 71237983(R)-4-((R)-1-(7-phenylquinolin-5-yloxy)ethyl)pyrrolidin-2-oneYield 17.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

30 mg of 7-Phenylquinolin-5-ol, 32.5 mg of (R)-4-((S)-1-hydroxyethyl)-1-((R)-1-phenylethyl)pyrrolidin-2-one and 150 mg of triphenylphosphine were dissolved in 3 mL of DCM. 125.5 mg of Di-tertbutyl-azodicarboxylate (DBAD) was added and the mixture stirred for 21 h at room temperature. The mixture was diluted with DCM and extracted with 1N NaOH and water. The organic phase was concentrated in vacuo and purified via flash column chromatography (FCC) (20 SiO2; cyclohexane→cyclohexane: ethylacetate: MeOH 58:40:2). Product containing fractions were concentrated, dissolved in 2 mL of trifluoroacetic acid (TFA) and heated 45 min at 150° C. in the microwave. The mixture was purified with rpHPLC (XbridgeC18, MeOH/water, TFA) to yield after lyophilisation 8 mg of Example 1 as solid.

Workup

  1. extractionextracted with 1N NaOH and water
  2. concentrationThe organic phase was concentrated in vacuo
  3. custompurified via flash column chromatography (FCC) (20 SiO2; cyclohexane→cyclohexane: ethylacetate: MeOH 58:40:2)
  4. additionProduct containing fractions
  5. concentrationwere concentrated
  6. dissolutiondissolved in 2 mL of trifluoroacetic acid (TFA)
  7. temperatureheated 45 min at 150° C. in the microwave
  8. customThe mixture was purified with rpHPLC (XbridgeC18, MeOH/water, TFA)

Sources & evidence

ORD record
ord-2d92025ac2a148a38553d64b99b3f751
Source dataset
uspto-grants-2015_12
Patent number
US09199937B2

Reaction notes

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