Dimethylformamide → HCID 15520892, compound

HRID 565135Notes

Reaction equation

HRID 565135 reaction equation
[H-].[Na+].CN(C)C=O.[C:8]([NH:15][C:16]1[C:17](=[CH:21][C:22]([OH:25])=[CH:23][CH:24]=1)[C:18]([OH:20])=[O:19])([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[CH2:26](Br)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(O)(=O)C>[C:8]([NH:15][C:16]1[C:17](=[CH:21][C:22]([O:25][CH2:18][C:17]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:16]=2)=[CH:23][CH:24]=1)[C:18]([O:20][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:19])([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7498Benzyl Bromide2×HCID 24758Sodium hydrideHCID 2757220n-boc-5-hydroxyanthranilic acid

Product 1

HCID 15520892HCID 15520892, compoundYield 56.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Sodium hydride (95%, 36.2 g, 1.51 mol) was placed into a dry 5 liter 3-necked round bottom flask under an atmosphere of argon. Anhydrous dimethylformamide (DMF) (2.0 liters) was added via canula followed by the careful addition of N-Boc-5-hydroxyanthranilic acid (150 g, 0.59 mol). The reaction mixture was cooled with an ice/water bath and benzyl bromide (148 mL, 1.24 mol) was added via syringe keeping the reaction temperature below 50° C. After addition was complete, the reaction mixture was stirred at 45° C.-50° C. for 6 hours. At this time additional benzyl bromide (35 mL, 0.29 mol) was added and the reaction continued at 45° C.-50° C. for an additional 2 hours. Acetic acid (20 mL) was carefully added and the reaction mixture was transferred to a round bottom flask and concentrated to a volume of approximately 400 mL. Ethyl acetate (1.0 liters) was added and the resulting solution was decanted from any solids present. The flask was rinsed with additional ethyl acetate (2×500 mL), decanting after each rinse. The combined organics were washed with water (1.0 liter) and saturated NaCl (500 mL). The organics were filtered and concentrated in vacuo to yield crude N-Boc-5-benzyloxyanthranilic acid, benzyl ester as a reddish brown syrup. The crude product was transferred to boiling hexanes (3 liters) and refluxed an additional 10 minutes. The solution was filtered while still hot and allowed to cool for 48 hours to yield 72 g of product (28% yield).

Workup

  1. temperatureThe reaction mixture was cooled with an ice/water bath
  2. customthe reaction temperature below 50° C
  3. additionAfter addition
  4. waitthe reaction continued at 45° C.-50° C. for an additional 2 hours
  5. customthe reaction mixture was transferred to a round bottom flask
  6. concentrationconcentrated to a volume of approximately 400 mL
  7. additionEthyl acetate (1.0 liters) was added
  8. customthe resulting solution was decanted from any solids present
  9. washThe flask was rinsed with additional ethyl acetate (2×500 mL)
  10. customdecanting after each rinse
  11. washThe combined organics were washed with water (1.0 liter) and saturated NaCl (500 mL)
  12. filtrationThe organics were filtered
  13. concentrationconcentrated in vacuo
  14. customto yield crude N-Boc-5-benzyloxyanthranilic acid, benzyl ester as a reddish brown syrup
  15. temperaturerefluxed an additional 10 minutes
  16. filtrationThe solution was filtered while still hot and
  17. temperatureto cool for 48 hours

Sources & evidence

ORD record
ord-2fa70b86fea6458d92f32a7029089e88
Source dataset
uspto-grants-2001_01
Patent number
US06171578B2

Reaction notes

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