Phthalic Anhydride → 2-(3-(Tert-butoxycarbonyl)phenyl)-3-methylpyridine 1-oxide

HRID 402555

Reaction equation

HRID 402555 reaction equation
[C:1]([O:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][N:14]=2)[CH:8]=1)([CH3:4])([CH3:3])[CH3:2].NC(N)=[O:23].OO.C1(=O)OC(=O)C2=CC=CC=C12.[O-]S([O-])=O.[Na+].[Na+].C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=O.O>[C:1]([O:5][C:6]([C:7]1[CH:8]=[C:9]([C:13]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][N+:14]=2[O-:23])[CH:10]=[CH:11][CH:12]=1)=[O:20])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 6811Phthalic Anhydride2×HCID 10340Sodium CarbonateHCID 24437Sodium Sulfite2×HCID 31294Carbamide PeroxideHCID 57516851tert-Butyl 3-(3-methylpyridin-2-yl)benzoate

Product 1

HCID 584883712-(3-(Tert-butoxycarbonyl)phenyl)-3-methylpyridine 1-oxideYield 95%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

tert-Butyl-3-(3-methylpyridin-2-yl)benzoate (1.0 eq) was dissolved in EtOAc (6 vol). Water (0.3 vol) was added, followed by urea-hydrogen peroxide (3 eq). Phthalic anhydride (3 eq) was then added portionwise to the mixture as a solid at a rate to maintain the temperature in the reactor below 45° C. After completion of the phthalic anhydride addition, the mixture was heated to 45° C. After stirring for an additional 4 hours, the heat was turned off. 10% w/w aqueous Na2SO3 (1.5 eq) was added via addition funnel. After completion of Na2SO3 addition, the mixture was stirred for an additional 30 minutes, and the layers separated. The organic layer was stirred, and 10% wt/wt aqueous. Na2CO3 (2 eq) was added. After stirring for 30 minutes, the layers were allowed to separate. The organic phase was washed 13% w/v aq NaCl. The organic phase was then filtered and concentrated to afford crude 2-(3-(tert-butoxycarbonyl)phenyl)-3-methylpyridine-1-oxide (95%) that was used directly in the next step.

Workup

  1. temperatureto maintain the temperature in the reactor below 45° C
  2. stirringthe mixture was stirred for an additional 30 minutes
  3. customthe layers separated
  4. stirringThe organic layer was stirred
  5. stirringAfter stirring for 30 minutes
  6. customto separate
  7. washThe organic phase was washed 13%
  8. filtrationThe organic phase was then filtered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c7d12dac8bdc4577808ab3df38b69548
Source dataset
uspto-grants-2014_06
Patent number
US08742122B2

Linked notes

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