Trimethylphosphine → triethyl [1-[(3-iodophenyl)methyl]-2-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-yl]methanetricarboxylate

HRID 1946550Notes

Reaction equation

HRID 1946550 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[C:13]3[CH:14](O)[CH2:15][CH2:16][CH2:17][C:12]=3[N:11]=[C:10]2[CH:19]([CH3:21])[CH3:20])[CH:5]=[CH:6][CH:7]=1.[CH:22]([C:33]([O:35][CH2:36][CH3:37])=[O:34])([C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:23]([O:25][CH2:26][CH3:27])=[O:24].CP(C)C.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1(C)C=CC=CC=1.CC1CCCO1.ClCCl>[I:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[C:13]3[CH:14]([C:22]([C:33]([O:35][CH2:36][CH3:37])=[O:34])([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:15][CH2:16][CH2:17][C:12]=3[N:11]=[C:10]2[CH:19]([CH3:21])[CH3:20])[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 68983TrimethylphosphineHCID 80471Triethyl methanetricarboxylateHCID 5363146Diisopropyl azodicarboxylateHCID 584601541-[(3-iodophenyl)methyl]-2-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-ol

Product 1

HCID 58460214triethyl [1-[(3-iodophenyl)methyl]-2-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-yl]methanetricarboxylate

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of Intermediate 91 (5.7 g) in Toluene (50 mL) and 2-Methyltetrahydrofuran (2-MeTHF) (50 mL) under nitrogen was added triethyl methanetricarboxylate (6.14 mL) followed by trimethylphosphine (2.54 mL). The reaction mixture was then cooled to −78° C. and DIAD (5.68 mL) was added dropwise over 12 min. The reaction mixture was allowed to continue stirring at −78° C. and under nitrogen for a further 40 min. The reaction mixture was then allowed to warm to room temperature and allowed to stir for a further 2 hours while still under nitrogen. The reaction mixture was then concentrated in vacuo before being partitioned between DCM (50 mL) and water (50 mL). The phases were separated and the aqueous layer was washed with further DCM (2×50 mL). The organic phases were combined, filtered through a hydrophobic frit and concentrated in vacuo to give 19.8 g of crude product as an orange oil. The sample was loaded in dichloromethane and purified on by column chromatography (silica) using a 0-100% ethyl acetate-cyclohexane gradient. The appropriate fractions were combined and evaporated in vacuo to give the required product 7.67 g as an off-white solid. LC/MS MH+ 611, Rt 3.54 min (5 min run).

Workup

  1. temperatureto warm to room temperature
  2. stirringto stir for a further 2 hours while still under nitrogen
  3. concentrationThe reaction mixture was then concentrated in vacuo
  4. custombefore being partitioned between DCM (50 mL) and water (50 mL)
  5. customThe phases were separated
  6. washthe aqueous layer was washed with further DCM (2×50 mL)
  7. filtrationfiltered through a hydrophobic frit
  8. concentrationconcentrated in vacuo
  9. customto give 19.8 g of crude product as an orange oil
  10. custompurified on by column chromatography (silica)
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-11ecbe747fbb4452b90bbdeb9b3f3f7a
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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