Ethyl Acetate → HCID 71227140, compound

HRID 715517Notes

Reaction equation

HRID 715517 reaction equation
COC1C=CC(C[N:10]2[CH2:14][C:13]3([CH2:19][CH2:18][CH2:17][C:16]([CH2:29][N:30]4[C:34]5[CH:35]=[C:36]([C:39]#[N:40])[CH:37]=[CH:38][C:33]=5[N:32]=[CH:31]4)([CH2:20][O:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:15]3)[O:12][C:11]2=[O:41])=CC=1.C(OCC)(=O)C.[OH-].[Na+]>C(#N)C>[O:41]=[C:11]1[NH:10][CH2:14][C:13]2([CH2:19][CH2:18][CH2:17][C:16]([CH2:29][N:30]3[C:34]4[CH:35]=[C:36]([C:39]#[N:40])[CH:37]=[CH:38][C:33]=4[N:32]=[CH:31]3)([CH2:20][O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:15]2)[O:12]1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 71116171HCID 71116171, compound

Product 1

HCID 71227140HCID 71227140, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a colorless solution of 1-[(3-{[4-(methyloxy)phenyl]methyl}-2-oxo-7-{[(phenylmethyl)oxy]methyl}-1-oxa-3-azaspiro[4.5]dec-7-yl)methyl]-1H-benzimidazole-6-carbonitrile (1.55 g, 2.81 mmol) in acetonitrile (28.1 mL) was added ceric ammonium nitrate (3.09 g, 5.63 mmol) and the mixture was stirred at room temperature. The reaction was then heated to 60° C. and stirred for 22 h. The reaction was then cooled to RT and the orange suspension was filtered using Buchner vacuum filtration. The solid was rinsed with MeCN (3×20 mL) and the filtrate concentrated to yield a glassy orange oil. Ethyl acetate (75 mL) and 2 N NaOH (50 mL) were then added. The mixture was filtered using Buchner vacuum filtration. The filtrate layers were separated and the aqueous layer was washed with EtOAc (50 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated. The concentrated organic layer was loaded onto florisil and purified using silica gel chromatography CISCO): 1-4% methanol/dichloromethane (25 min), 40 g silica. The product eluted at 11 minutes to yield 1-[(2-oxo-7-{[(phenylmethyl)oxy]methyl}-1-oxa-3-azaspiro[4.5]dec-7-yl)methyl]-1H-benzimidazole-6-carbonitrile as a orange foam (653 mg, 51% yield). MS (m/z) 431.0 (M+H+).

Workup

  1. temperatureThe reaction was then heated to 60° C.
  2. stirringstirred for 22 h
  3. temperatureThe reaction was then cooled to RT
  4. filtrationthe orange suspension was filtered
  5. filtrationBuchner vacuum filtration
  6. washThe solid was rinsed with MeCN (3×20 mL)
  7. concentrationthe filtrate concentrated
  8. customto yield a glassy orange oil
  9. filtrationThe mixture was filtered
  10. filtrationBuchner vacuum filtration
  11. customThe filtrate layers were separated
  12. washthe aqueous layer was washed with EtOAc (50 mL)
  13. dry with materialThe combined organic layers were dried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated
  16. custompurified
  17. custom1-4% methanol/dichloromethane (25 min), 40 g silica
  18. washThe product eluted at 11 minutes

Sources & evidence

ORD record
ord-7ba2f4a222b145dfa860acfc2dbdeca8
Source dataset
uspto-grants-2015_11
Patent number
US09187464B2

Reaction notes

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