Sodium hydride → 1-tert-butyl-3-[(1S,2S)-2,3-dihydroxy-1-phenyl-propyl]-1,3-dihydro-2H-benzimidazol-2-one

HRID 2110386Notes

Reaction equation

HRID 2110386 reaction equation
[C:1]([N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[NH:7][C:6]1=[O:14])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[C:17]1([C@H:23]2[O:25][C@@H:24]2[CH2:26][OH:27])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C)C=O.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:1]([N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]([C@@H:23]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:24]([OH:25])[CH2:26][OH:27])[C:6]1=[O:14])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 150502((2R,3R)-3-phenyloxiran-2-yl)methanolHCID 133062921-Tert-butyl-1,3-dihydro-benzimidazol-2-one

Product 1

HCID 442547721-tert-butyl-3-[(1S,2S)-2,3-dihydroxy-1-phenyl-propyl]-1,3-dihydro-2H-benzimidazol-2-one

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 1-tert-butyl-1,3-dihydro-benzimidazol-2-one (0.66 g, 3.5 mmol) and sodium hydride (60% dispersion in mineral oil, 0.15 g, 3.8 mmol) in anhydrous dimethylformamide (4 mL) was stirred for 10 minutes under nitrogen at room temperature. A solution of [(2R,3R)-3-phenyloxiran-2-yl]methanol (EXAMPLE 117, step 4, 1.07 g, 7.1 mmol) and titanium isopropoxide (2.14 mL, 7.1 mmol) in dimethylformamide (4 mL) that was aged for 20 minutes was then added and the mixture was stirred at room temperature under nitrogen for 12 hours. After disappearance of the epoxide, the mixture was partitioned between a 1N aqueous solution of hydrochloric acid (50 mL) and ethyl acetate (50 mL). The organic layer was separated, washed with saturated sodium bicarbonate (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel column (60% ethyl acetate in hexane) to give 1-tert-butyl-3-[(1S,2S)-2,3-dihydroxy-1-phenyl-propyl]-1,3-dihydro-2H-benzimidazol-2-one as an oil. MS (ES) m/z 341.2.

Workup

  1. additionwas then added
  2. stirringthe mixture was stirred at room temperature under nitrogen for 12 hours
  3. customAfter disappearance of the epoxide, the mixture was partitioned between a 1N aqueous solution of hydrochloric acid (50 mL) and ethyl acetate (50 mL)
  4. customThe organic layer was separated
  5. washwashed with saturated sodium bicarbonate (50 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified via silica gel column (60% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-ee3925a5d7f941c8a99f322faf041315
Source dataset
uspto-grants-2009_04
Patent number
US07517899B2

Reaction notes

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