Ethyl Acetate → tert-Butyl{(1R)-2-[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)oxy]-1-phenylethyl}carbamate

HRID 1038974Notes

Reaction equation

HRID 1038974 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[NH2:25])[O:5][CH2:6][C@H:7]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C1N=CN([C:31](N2C=NC=C2)=[O:32])C=1.C(OCC)(=O)C.C([O-])(O)=O.[Na+]>CN(C=O)C>[O:32]=[C:31]1[NH:25][C:24]2[CH:23]=[CH:22][C:4]([O:5][CH2:6][C@H:7]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)=[CH:3][C:2]=2[NH:1]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 682631,1'-CarbonyldiimidazoleHCID 516892Sodium BicarbonateHCID 58443062tert-butyl [(1R)-2-(3,4-diaminophenoxy)-1-phenylethyl]carbamate2×

Product 1

HCID 68240928tert-Butyl{(1R)-2-[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)oxy]-1-phenylethyl}carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

tert-Butyl [(1R)-2-(3,4-diaminophenoxy)-1-phenylethyl]carbamate (Intermediate 6) (318 mg, 0.93 mmol) was placed in a 50-mL RBF under a nitrogen atmosphere and dissolved in DMF (5 mL). CDI (135 mg, 0.83 mmol) was added, and the reaction was stirred at room temperature for four hours. The reaction was added to a separatory funnel containing ethyl acetate (125 mL) and dilute aqueous NaHCO3 (75 mL); the phases were separated, and the organic layer was washed with brine (75 mL), dried over anhydrous Na2SO4 and then concentrated in vacuo. The crude product mixture was then purified by silica gel chromatography to afford tert-butyl {(1R)-2-[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)oxy]-1-phenylethyl}carbamate as a white solid. 1H NMR (500 MHz, C2D6SO) δ 10.49 (s, 1H), 10.37 (s, 1H), 7.54 (d, 1H), 7.34 (m, 4H), 7.25 (t, 1H), 6.77 (d, 1H), 6.48 (s, 2H), 4.86 (q, 1H), 3.98 (m, 2H), 1.37 (s, 9H). LRMS (ESI) calc'd for (C16H16N3O4) [M−C4H8+H]+, 314.1; found 314.1.

Workup

  1. additionThe reaction was added to a separatory funnel
  2. customthe phases were separated
  3. washthe organic layer was washed with brine (75 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product mixture was then purified by silica gel chromatography

Sources & evidence

ORD record
ord-197479e5642643c6b4a7bc3d6844d74c
Source dataset
uspto-grants-2013_10
Patent number
US08552019B2

Reaction notes

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