Benzyl chloroformate → HCID 69916010, compound

HRID 582230Notes

Reaction equation

HRID 582230 reaction equation
[C:1]1([CH2:7][O:8][C:9]([N:11]2[CH2:20][CH2:19][N:18]3[CH:13]([CH2:14][O:15][C:16]4[CH:24]=[C:23]([N+:25]([O-])=O)[CH:22]=[CH:21][C:17]=43)[CH2:12]2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])=O.[NH4+].C(=O)([O-])[O-].[K+].[K+].[CH2:38]([O:45][C:46](Cl)=[O:47])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>O1CCCC1.CO.[Pd]>[C:1]1([CH2:7][O:8][C:9]([N:11]2[CH:20]=[CH:19][N:18]3[C:13](=[CH:14][O:15][C:16]4[CH:24]=[C:23]([NH:25][C:46]([O:45][CH2:38][C:39]5[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=5)=[O:47])[CH:22]=[CH:21][C:17]=43)[CH2:12]2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 4

HCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 2723923Ammonium formateHCID 86754234HCID 86754234, compound

Product 1

HCID 69916010HCID 69916010, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a flask containing 1, 2, 4a, 5-tetrahydro-8-nitro-pyrazino[2, 1-c] [1, 4]benzoxazine-3(4 H)-carboxylic acid phenylmethyl ester (Step 6, 2.75 g, 7.45 mmol) in tetrahydrofuran (100 mL) and methanol (50 mL) is added 10% palladium on carbon (2.00 g) and ammonium formate (4.69 g, 74.45 mmol), heated to reflux for 2 hours and stirred at ambient temperature for 15 hours. The mixture is filtered through celite and concentrated in vacuo. To the residue dissolved in water (15 mL) and acetone (15 mL) cooled to 0° C. is added potassium carbonate (2.27 g, 16.39 mmol) followed by benzyloxycarbonylchloride (2.34 mL, 16.39 mmol). The reaction is slowly warmed to ambient temperature, stirred for 64 hours, concentrated in vacuo, diluted with ethyl acetate (100 mL), washed with water (2×25 mL) and saline, dried over Na2SO4, concentrated in vacuo and chromatographed on silica gel (230-400 mesh, 200 mL), eluting with hexane/ethyl acetate (75/25). The appropriate fractions are combined (Rf =0.46, TLC, hexane/ethyl acetate, 50/50) and concentrated in vacuo to give the title compound, mp 118-120° C.

Workup

  1. temperatureheated
  2. temperatureto reflux for 2 hours
  3. filtrationThe mixture is filtered through celite and
  4. concentrationconcentrated in vacuo
  5. dissolutionTo the residue dissolved in water (15 mL)
  6. temperatureacetone (15 mL) cooled to 0° C.
  7. temperatureThe reaction is slowly warmed to ambient temperature
  8. stirringstirred for 64 hours
  9. concentrationconcentrated in vacuo
  10. additiondiluted with ethyl acetate (100 mL)
  11. washwashed with water (2×25 mL) and saline
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated in vacuo
  14. customchromatographed on silica gel (230-400 mesh, 200 mL)
  15. washeluting with hexane/ethyl acetate (75/25)
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e398a1271a134cc48605a0d79f6cbd55
Source dataset
uspto-grants-1999_07
Patent number
US05922707

Reaction notes

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