HCID 56655506, compound → HCID 68046642, compound

HRID 882211Notes

Reaction equation

HRID 882211 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([C:10]2[CH:25]=[CH:24][C:13]3[N:14]([CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C:15](=[O:18])[N:16]([CH3:17])[C:12]=3[CH:11]=2)[CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].[C:26]1([Mg]Cl)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1COCC1>[CH3:22][C:20]([CH3:21])([CH3:23])[CH2:19][N:14]1[C:13]2[CH:24]=[CH:25][C:10]([C:6]3[CH:7]=[CH:8][CH:9]=[C:4]([C:1]([OH:3])([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH3:2])[CH:5]=3)=[CH:11][C:12]=2[N:16]([CH3:17])[C:15]1=[O:18]

Participants

4

Reactant 2

HCID 56655506HCID 56655506, compoundHCID 178478979HCID 178478979, compound

Product 1

HCID 68046642HCID 68046642, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-(3-acetylphenyl)-1-(2,2-dimethylpropyl)-3-methyl-1,3-dihydro-2H-benzimidazol-2-one (1-17, 170 mg, 0.51 mmol) in anhydrous THF (5 ml) was cooled to −78 deg C. and treated with Phenyl magnesium chloride (1.8 M in THF, 365 μL, 0.66 mmol, 1.3 eq). The reaction mixture was warmed to 0 deg C. and stirred for 1 h. The reaction was only ˜30% complete, so more of the Grignard reagent (1.8 M in THF, 365 μL, 0.66 mmol, 1.3 eq) was added at 0 deg C. and the reaction was maintained there for 30 min. The completed reaction was partitioned between EtOAc (50 ml) and water (55 ml) and the cloudy, white precipitate present which was removed via filtration. The filtrate was separated in a separatory funnel and the aqueous layer was re-extracted with EtOAc (50 ml). The combined organic layers were dried over Na2SO4, concentrated, then purified via flash column chromatography (SiO2: 100% Hex to 50:50 Hex/EtOAc), affording the title compound, 1-(2,2-dimethylpropyl)-5-[3-(1-hydroxy-1-phenylethyl)phenyl]-3-methyl-1,3-dihydro-2H-benzimidazol-2-one (10-1) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.70 (s, 1H), 7.48-7.45 (m, 3H), 7.40-7.31 (m, 4H), 7.27-7.24 (m, 2H), 7.12 (s, 1H), 7.05 (d, 1H, J=8.15 Hz), 3.67 (s, 2H), 3.45 (s, 3H), 2.02 (s, 3H), 1.05 (s, 9H). LRMS m/z: Calc'd for C27H30N2O2(M+H) 415.2, found 415.5.

Workup

  1. temperatureThe reaction mixture was warmed to 0 deg C
  2. temperatureand the reaction was maintained there for 30 min
  3. customThe completed reaction
  4. customwas partitioned between EtOAc (50 ml) and water (55 ml)
  5. customthe cloudy, white precipitate present which was removed via filtration
  6. customThe filtrate was separated in a separatory funnel
  7. extractionthe aqueous layer was re-extracted with EtOAc (50 ml)
  8. dry with materialThe combined organic layers were dried over Na2SO4
  9. concentrationconcentrated
  10. custompurified via flash column chromatography (SiO2: 100% Hex to 50:50 Hex/EtOAc)

Sources & evidence

ORD record
ord-83e82d49ba5d4b49a29da0d1ccf4a015
Source dataset
uspto-grants-2015_03
Patent number
US08993779B2

Reaction notes

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