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

HRID 1402710ノート

反応式

HRID 1402710 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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. Analysis: HPLC-MS: Rt=1.21 min (method D), M+H=333.

後処理

  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)

出典と根拠

ORDレコード
ord-3e3a4298db8143d78af19d38cb34d5ca
出典データセット
uspto-grants-2014_12
特許番号
US08912173B2

反応ノート

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