Metaperiodic acid → 4-Allyl-5-methyl-3-styryl-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one

HRID 584779Notes

Reaction equation

HRID 584779 reaction equation
[CH2:1]([NH:4][CH:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[NH:13][C:14](=[O:21])[CH:15](O)[C:16](O)([CH3:18])C)[CH3:6])[CH:2]=[CH2:3].I(O)(=O)(=O)=O.[C:27]1(/C=C/B(O)O)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CO.O.C(OCC)(=O)C>[CH2:1]([N:4]1[CH:5]([CH3:6])[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[NH:13][C:14](=[O:21])[CH:15]1[CH:16]=[CH:18][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH:2]=[CH2:3]

Participants

7

Reactant 3

HCID 65185Metaperiodic acidHCID 5702628Styrylboronic acidHCID 22341801N-[2-(1-Allylamino-ethyl)-phenyl]-2,3-dihydroxy-3-methyl-butyramide

Product 1

HCID 697312034-Allyl-5-methyl-3-styryl-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-oneYield 81%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

The product of Example 14 (117 mg, 0.4 mmol) was placed in a 25 mL round bottom flask and dissolved in methanol (2 mL) and water (1 mL). To this solution was added periodic acid (192 mg, 0.84 mmol), and the mixture was allowed to stir at room temperature for 2 hours. After this time, the solvent was then evaporated and the resulting residue was taken up in ethyl acetate (20 mL) and transferred to a separatory funnel. The organic layer was then washed with a saturated sodium bicarbonate solution (5×15 mL) until the aqueous layer no longer turned pink in color. The organic layer was then washed with brine (1×15 mL), dried over magnesium sulfate, filtered and evaporated. This resulting aminol was then dissolved in acetonitrile (4 mL) and to this solution was added (E)-2-Phenylvinylboronic acid (75 mg, 0.5 mmol), and the solution was brought to reflux for 4 hours. After this time, the reaction was diluted with ethyl acetate (40 mL), and transferred to a separatory funnel. The organic layer was washed with 1N NaOH (3×15 mL), brine (1×15 mL), dried over magnesium sulfate, filtered, and evaporated to yield the desired product, and an isomeric by-product in a combined yield of 81%. 1H NMR was used to estimate the ratio of product to by-product to be approximately 77:23. This mixture was taken crude to the next transformation to avoid further isomerization upon isolation. 1H NMR (250 MHz, CDCl3, major isomer) δ 7.75 (bs, 1H), 7.43-7.37 (m, 2H), 7.33-7.15 (m, 6H), 7.11-7.04 (m, 1H), 6.85-6.82 (m, 1H), 6.57 (dd, J=16.0 Hz, J=4.8 Hz, 1H), 5.92-5.69 (m, 1H), 5.18-5.03 (m, 2H), 4.44-4.39 (m, 1H), 4.29 (q, J=6.6 Hz, 1H), 3.27-3.16 (m, 1H), 2.92-2.80 (m, 1H), 1.55 (d, J=6.6 Hz, 3H).

Workup

  1. customAfter this time, the solvent was then evaporated
  2. customtransferred to a separatory funnel
  3. washThe organic layer was then washed with a saturated sodium bicarbonate solution (5×15 mL) until the aqueous layer no longer turned pink in color
  4. washThe organic layer was then washed with brine (1×15 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThis resulting aminol was then dissolved in acetonitrile (4 mL) and to this solution
  9. temperatureto reflux for 4 hours
  10. customtransferred to a separatory funnel
  11. washThe organic layer was washed with 1N NaOH (3×15 mL), brine (1×15 mL)
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. customevaporated

Sources & evidence

ORD record
ord-ef5332bc07964895b4f3f4e297fa3fc7
Source dataset
uspto-grants-2005_08
Patent number
US06927294B1

Reaction notes

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