Triphenylphosphine → (R)-4-((R)-1-((5-bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

HRID 2209039ノート

反応式

HRID 2209039 の反応式
[Br:1][C:2]1[CH:13]=[C:12]([OH:14])[C:5]2[N:6]([CH:9]3[CH2:11][CH2:10]3)[CH:7]=[N:8][C:4]=2[CH:3]=1.O[C@H:16]([C@H:18]1[CH2:22][N:21]([C@@H:23]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[CH3:24])[C:20](=[O:33])[CH2:19]1)[CH3:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[Br:1][C:2]1[CH:13]=[C:12]([O:14][C@@H:16]([C@H:18]2[CH2:22][N:21]([C@@H:23]([C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)[CH3:24])[C:20](=[O:33])[CH2:19]2)[CH3:17])[C:5]2[N:6]([CH:9]3[CH2:11][CH2:10]3)[CH:7]=[N:8][C:4]=2[CH:3]=1

参加物

6

反応物 4

HCID 11776Triphenylphosphine2 回HCID 220568ethyl N-ethoxycarbonyliminocarbamate2 回HCID 71238294(4R)-4-[(1S)-1-hydroxyethyl]-1-[(1R)-1-(4-methoxyphenyl)ethyl]pyrrolidin-2-one2 回HCID 1178436505-Bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-ol

生成物 1

HCID 117844014(R)-4-((R)-1-((5-bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

5-bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-ol 2.73 (1.4 g, 5.53 mmol), (R)-4-((S)-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin- 2-one 1.05 (2.04 g, 7.75 mmol), and triphenylphosphine (2.04 g, 7.78 mmol) were taken up in THF (30 mL). Diethyl azodicarboxylate (1.2 ml, 7.65 mmol) was added dropwise over 1 min, and the resulting stirred solution was heated to 40 C. After 1 h, add additional portions of intermediate 1.05 (0.27 g, 1.02 mmol), triphenylphosphine (0.27 g, 1.02 mmol), and diethyl azodicarboxylate (0.15 ml, 0.96 mmol) were added. The mixture was stirred an additional 1.5 h and was then concentrated directly onto silica gel. Purification by silica gel chromatography (20-100% acetone:hexanes) provided (R)-4-((R)-1-((5-bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one (2.74). LCMS-ESI+ (m/z): [M+H]+ calcd for C25H29BrN3O3: 498.14; found: 498.37.

後処理

  1. temperaturewas heated to 40 C
  2. additionwere added
  3. stirringThe mixture was stirred an additional 1.5 h
  4. concentrationwas then concentrated directly onto silica gel
  5. customPurification by silica gel chromatography (20-100% acetone:hexanes)

出典と根拠

ORDレコード
ord-d4bf033951e94bc0948331d4ec37fb8b
出典データセット
uspto-grants-2016_06
特許番号
US09376441B2

反応ノート

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