Nitric Acid → HCID 19045439, compound

HRID 1781406Notes

Reaction equation

HRID 1781406 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[CH2:19][CH2:18][C:13]3([O:17][CH2:16][CH2:15][O:14]3)[CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[C:20]([O:23]C(=O)C)(=O)[CH3:21].[N+:27]([O-])([OH:29])=[O:28]>C(Cl)Cl.[Cl-].[Na+].O>[C:13]([OH:17])(=[O:14])[CH3:12].[NH:1]([C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[CH2:19][CH2:18][C:13]3([O:17][CH2:16][CH2:15][O:14]3)[CH2:12][CH2:11]2)=[CH:4][C:3]=1[N+:27]([O-:29])=[O:28])[C:20]([CH3:21])=[O:23]

Participants

6

Reactant 3

HCID 944Nitric AcidHCID 7918Acetic Anhydride2×HCID 19045214HCID 19045214, compound

Product 1

HCID 19045439HCID 19045439, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-5 °C

Procedure

A mechanically stirred solution of N(2-(4-aminophenyl)ethyl)-1,4-dioxa-8-azaspiro[4.5]-decane in methylene chloride (400 mL) cooled to -5° C. under an argon atmosphere was treated dropwise with acetic anhydride (58.8 mL, 622 mmoles). The reaction was allowed to reach room temperature and was stirred for 18 hr. After the addition of an additional 29.5 mL (312 mmoles) of acetic anhydride, the reaction was cooled to -5° C., and a solution of nitric acid (d=1.49, 22.0 mL, 468 mmoles) in methylene chloride (1:1 by volume) was added dropwise. The reaction mixture was allowed to reach room temperature and was stirred for 4 hours. The mixture was cooled in an ice bath and 100 mL of saturated brine was added. The layers were separated and the aqueous phase was extracted with methylene chloride. The combined organic portion was dried (Na2SO4), concentrated and flushed with toluene (3×200 mL). The crude product crystallized during concentration, was filtered, and triturated with ethyl acetate (550 mL) to yield 56.7 g (89%) of N(2-(4-acetamino-3-nitrophenyl)ethyl)-1,4-dioxa-8-azaspiro[4.5]-decane acetic acid salt. TLC Rf=0.80 (silica gel, 5% methanol in methylene chloride saturated with ammonia).

Workup

  1. customto reach room temperature
  2. customto reach room temperature
  3. stirringwas stirred for 4 hours
  4. temperatureThe mixture was cooled in an ice bath
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted with methylene chloride
  7. dry with materialThe combined organic portion was dried (Na2SO4)
  8. concentrationconcentrated
  9. customflushed with toluene (3×200 mL)
  10. customThe crude product crystallized during concentration
  11. filtrationwas filtered
  12. customtriturated with ethyl acetate (550 mL)

Sources & evidence

ORD record
ord-a2c1a5bf1f6c453393f3e3747eac03ce
Source dataset
uspto-grants-1997_05
Patent number
US05633247

Reaction notes

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