Trimethylphosphine → Triethyl [1-[(4-chlorophenyl)methyl]-2-(1,1-dimethylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-yl]methanetricarboxylate

HRID 1946518Notes

Reaction equation

HRID 1946518 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([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[C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:4][CH:3]=1.[CH2:23]([O:25][C:26]([CH:28]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:29]([O:31][CH2:32][CH3:33])=[O:30])=[O:27])[CH3:24].CP(C)C.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1(C)C=CC=CC=1.O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[C:13]3[CH:14]([C:28]([C:34]([O:36][CH2:37][CH3:38])=[O:35])([C:26]([O:25][CH2:23][CH3:24])=[O:27])[C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:15][CH2:16][CH2:17][C:12]=3[N:11]=[C:10]2[C:19]([CH3:21])([CH3:22])[CH3:20])=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 68983TrimethylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 80471Triethyl methanetricarboxylateHCID 584601821-[(4-chlorophenyl)methyl]-2-(1,1-dimethylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-ol

Product 1

HCID 58460179Triethyl [1-[(4-chlorophenyl)methyl]-2-(1,1-dimethylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-yl]methanetricarboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of Intermediate 54 (82 mg) and triethylmethanetricarboxylate (0.11 mL) in anhydrous toluene (3 mL) and anhydrous tetrahydrofuran (3.00 mL) under a nitrogen atmosphere was added trimethylphosphine, 1M in toluene (0.52 mL). The reaction was then cooled to −78° C. and diisopropyl azodicarboxylate (0.11 mL) added dropwise via syringe over 1 min. The reaction was stirred at −78° C. under an atmosphere of nitrogen for 60 mins before being allowed to warm to ambient temperature and stirred for a further 16 hr. The reaction was concentrated in vacuo. The residue was taken up in dichloromethane (40 mL) and washed with water (40 mL), dried (hydrophobic frit) and concentrated in vacuo. The sample was loaded in dichloromethane and purified on silica 0-100% ethyl acetate-cyclohexane gradient. The appropriate fractions were combined and evaporated in vacuo to give the required product (100 mg). LC/MS MH+533, Rt 2.18 mins (5 min run).

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred for a further 16 hr
  3. concentrationThe reaction was concentrated in vacuo
  4. washwashed with water (40 mL)
  5. customdried (hydrophobic frit)
  6. concentrationconcentrated in vacuo
  7. custompurified on silica 0-100% ethyl acetate-cyclohexane gradient
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-94754a1ca8724030a3b08b4fc3b280aa
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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