Triphenylphosphine → (R)-4-((R)-1-(7-(3,4,5-trimethoxyphenyl)quinolin-5-yloxy)ethyl)pyrrolidin-2-one

HRID 1402711Notes

Reaction equation

HRID 1402711 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[CH:14]=[C:15]([OH:23])[C:16]3[CH:17]=[CH:18][CH:19]=[N:20][C:21]=3[CH:22]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].O[C@H:25]([C@H:27]1[CH2:31][N:30]([C@@H](C2C=CC=CC=2)C)[C:29](=[O:40])[CH2:28]1)[CH3:26].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1C=CC(COC(/N=N/C(OCC2C=CC=CC=2)=O)=O)=CC=1>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[CH:22]=[C:21]3[C:16]([CH:17]=[CH:18][CH:19]=[N:20]3)=[C:15]([O:23][C@@H:25]([C@H:27]3[CH2:31][NH:30][C:29](=[O:40])[CH2:28]3)[CH3:26])[CH:14]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5387121Dibenzyl azodicarboxylateHCID 58072048(R)-4-((S)-1-hydroxyethyl)-1-((R)-1-phenylethyl)pyrrolidin-2-oneHCID 1364132517-(3,4,5-Trimethoxyphenyl)quinolin-5-ol

Product 1

HCID 71238463(R)-4-((R)-1-(7-(3,4,5-trimethoxyphenyl)quinolin-5-yloxy)ethyl)pyrrolidin-2-oneYield 19.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

80 mg of 7-(3,4,5-Trimethoxyphenyl)quinolin-5-ol, 62 mg of (R)-4-((S)-1-hydroxyethyl)-1-((R)-1-phenylethyl)pyrrolidin-2-one and 142 mg of triphenylphosphine was dissolved in 5 mL of DCM. 125.5 mg of DBAD was added and the mixture stirred for 6 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 chromatography (10 SiO2; cyclohexane→cyclohexane:ethylacetate:MeOH 58:40:2). Product containing fractions were concentrated, dissolved in 1.5 mL of TFA and heated 75 min at 150° C. in the microwave. The mixture was purified with HPLC (XbridgeC18, MeOH/water, TFA) to yield after lyophilisation 21 mg of Example 2 as solid.

Workup

  1. extractionextracted with 1N NaOH and water
  2. concentrationThe organic phase was concentrated in vacuo
  3. custompurified via flash chromatography (10 SiO2; cyclohexane→cyclohexane:ethylacetate:MeOH 58:40:2)
  4. additionProduct containing fractions
  5. concentrationwere concentrated
  6. dissolutiondissolved in 1.5 mL of TFA
  7. temperatureheated 75 min at 150° C. in the microwave
  8. customThe mixture was purified with HPLC (XbridgeC18, MeOH/water, TFA)

Sources & evidence

ORD record
ord-d5dceae502624bf6a040f76a02228659
Source dataset
uspto-grants-2014_12
Patent number
US08912173B2

Reaction notes

Loading…