Triethylamine → HCID 15520897, compound

HRID 565140Notes

Reaction equation

HRID 565140 reaction equation
[C:1]([CH2:8][NH:9][C:10]1[C:11](=[CH:15][C:16]([OH:19])=[CH:17][CH:18]=1)[C:12]([OH:14])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[C:20]([CH2:30][NH:31][CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])(OCC1C=CC=CC=1)=[O:21].C(N(CC)CC)C.[H][H]>CN(C=O)C.[Pd].C(OCC)(=O)C.CO>[C:1]([CH2:8][N:9]1[C:10]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][C:11]=2[C:12](=[O:14])[N:31]([CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:30][C:20]1=[O:21])([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 15520895HCID 15520895, compoundHCID 15520896HCID 15520896, compoundHCID 178418361HCID 178418361, compound2×

Product 1

HCID 15520897HCID 15520897, compoundYield 50%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

N-(Carbo-t-butoxymethyl)-5-hydroxyanthranilic acid (26.7 g, 100 mmol) was placed in a dry 2 liter round bottom flask. The reaction atmosphere was flushed with argon and N-(carbobenzyloxymethyl)-3-aminopropionic acid, ethyl ester (29.0 g, 109 mmol) in anhydrous DMF (500 mL) was added, followed by the addition of O-(7-azabenzotriaol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU reagent, 39.9 g, 105 mmol). Triethylamine (42.0 mL, 301 mmol) was added and the reaction mixture was stirred at room temperature under a balloon of argon for 16 hours. The DMF was removed in vacuo on a rotary evaporator and the residue partitioned between ethyl acetate (1.0 liter) and saturated NaHCO3 (500 mL). The organics were washed with water (500 mL), saturated NaCl (100 mL) and dried over MgSO4. The organics were filtered, the volatiles removed in vacuo on a rotary evaporator and the residual oil pumped on under high vacuum to yield an oil. This oil was taken up in 9:3 ethyl acetate/methanol (1200 mL) and placed under an atmosphere of argon gas. 10% Pd/C (4.0 g) was added and the reaction atmosphere replaced with hydrogen gas (4 purge-fills). The reaction mixture was stirred under a balloon of hydrogen for 45 hours. The reaction atmosphere was replaced with argon and the suspension filtered through a pad of Celite, which was washed with an additional 300 mL of methanol. The volatiles were removed in vacuo and the residue was taken up in a minimum of dichloromethane and chromatographed on silica gel, eluting the column with 1:1 ethyl acetate/hexanes. Fractions containing pure product (Rf=0.17 in 1:1 ethyl acetate/hexanes) were combined and the solvents removed in vacuo to yield 1-(carbo-t-butoxymethyl)-4-(2-carboethoxyethyl)-7-hydroxy-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione as a white solid (20.2 g, 50% yield).

Workup

  1. customThe reaction atmosphere
  2. additionwas added
  3. customThe DMF was removed in vacuo on a rotary evaporator
  4. customthe residue partitioned between ethyl acetate (1.0 liter) and saturated NaHCO3 (500 mL)
  5. washThe organics were washed with water (500 mL), saturated NaCl (100 mL)
  6. dry with materialdried over MgSO4
  7. filtrationThe organics were filtered
  8. customthe volatiles removed in vacuo on a rotary evaporator
  9. customto yield an oil
  10. customthe reaction atmosphere
  11. customThe reaction atmosphere
  12. filtrationthe suspension filtered through a pad of Celite, which
  13. washwas washed with an additional 300 mL of methanol
  14. customThe volatiles were removed in vacuo
  15. customchromatographed on silica gel
  16. washeluting the column with 1:1 ethyl acetate/hexanes
  17. additionFractions containing pure product (Rf=0.17 in 1:1 ethyl acetate/hexanes)
  18. customthe solvents removed in vacuo

Sources & evidence

ORD record
ord-a7853158ef13486cbc26a55fb37d01bd
Source dataset
uspto-grants-2001_01
Patent number
US06171578B2

Reaction notes

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