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

HRID 716617Notes

Reaction equation

HRID 716617 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) is dissolved in EtOAc (6 vol). Water (0.3 vol) is added followed by urea-hydrogen peroxide (3 eq). The phthalic anhydride (3 eq) is added portion-wise as a solid to maintain the temperature in the reactor below 45° C. After completion of phthalic anhydride addition, the mixture is heated to 45° C. After stirring for an additional 4 hours, the heat is turned off 10% w/w aqueous Na2SO3 (1.5 eq) is added via addition funnel. After completion of Na2SO3 addition, the mixture is stirred for an additional 30 minutes and the layers separated. The organic layer is stirred and 10% w/w aq. Na2CO3 (2 eq) is added. After stirring for 30 minutes, the layers are allowed to separate. The organic phase is washed 13% w/v aq NaCl. The organic phase is then filtered and concentrated to afford crude 2-(3-(tert-butoxycarbonyl)phenyl)-3-methylpyridine-1-oxide (95%) that is used directly in the next step.

Workup

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

Sources & evidence

ORD record
ord-a53ba03fe5c5419ca076ea1b2b5af0aa
Source dataset
uspto-grants-2015_11
Patent number
US09192606B2

Reaction notes

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