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 2209039Notes

Reaction equation

HRID 2209039 reaction equation
[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

Participants

6

Reactant 4

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

Product 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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-d4bf033951e94bc0948331d4ec37fb8b
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

Loading…