2,6-Lutidine → HCID 15520894, compound

HRID 565137Notes

Reaction equation

HRID 565137 reaction equation
C(=O)(O)[O-].[Na+].Cl.[CH2:7]([O:14][C:15]1[CH:30]=[C:19]([C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])[C:18]([NH2:31])=[CH:17][CH:16]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.N1C(C)=CC=CC=1C.Br[CH2:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43]>CN(C=O)C.C(OCC)(=O)C>[C:42]([CH2:41][NH:31][C:18]1[C:19](=[CH:30][C:15]([O:14][CH2:7][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:16][CH:17]=1)[C:20]([O:22][CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:21])([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43]

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 79177tert-Butyl bromoacetateHCID 516892Sodium BicarbonateHCID 131722256HCID 131722256, compound

Product 1

HCID 15520894HCID 15520894, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of saturated sodium bicarbonate (1.0 liter) was placed in a 4 liter Ehrlenmeyer flask along with 1.0 liter of ethyl acetate. The biphasic mixture was stirred at a rate that insured mixing and 5-benzyloxyanthranilic acid, benzyl ester, hydrochloride (50.0 g, 135 mmol) was added portionwise to the stirred mixture. After addition was complete, the mixture was stirred an additional 15 minutes. The layers were partitioned in a separatory funnel and the aqueous layer was extracted with ethyl acetate (500 mL). The combined organics were dried over MgSO4, filtered, and concentrated in vacuo to yield the free base, which was dissolved in anhydrous DMF (700 mL) under an atmosphere of argon. 2,6-lutidine (20.0 mL, 172 mmol) was added to the solution followed by the addition of t-butyl bromoacetate (29.0 mL, 196 mmol). The reaction mixture was stirred at 70° C. under an atmosphere of argon for 48 hours. The DMF was removed on a rotary evaporator under high vacuum and the crude product residue was partitioned between ethyl acetate (1.0 liter) and water (500 mL). The organic layer was washed with saturated NaCl (250 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to yield crude product as a light brown solid. The product was recrystallized from 7% ethyl acetate/hexanes to yield N-(carbo-t-butoxymethyl)-5-benzyloxyanthranilic acid, benzyl ester (46.4 g, 79% yield).

Workup

  1. additionthat insured mixing
  2. additionAfter addition
  3. stirringthe mixture was stirred an additional 15 minutes
  4. customThe layers were partitioned in a separatory funnel
  5. extractionthe aqueous layer was extracted with ethyl acetate (500 mL)
  6. dry with materialThe combined organics were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto yield the free base, which
  10. stirringThe reaction mixture was stirred at 70° C. under an atmosphere of argon for 48 hours
  11. customThe DMF was removed on a rotary evaporator under high vacuum
  12. customthe crude product residue was partitioned between ethyl acetate (1.0 liter) and water (500 mL)
  13. washThe organic layer was washed with saturated NaCl (250 mL)
  14. dry with materialdried over Na2SO4
  15. filtrationThe solution was filtered
  16. concentrationconcentrated in vacuo
  17. customto yield crude product as a light brown solid
  18. customThe product was recrystallized from 7% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-8bf1c97f494b450e93943cb88b3d5848
Source dataset
uspto-grants-2001_01
Patent number
US06171578B2

Reaction notes

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