Water → 5-(Di-tert-butoxycarbonylamino-methyl)-2-nitro-benzoic acid methyl ester

HRID 453015Notes

Reaction equation

HRID 453015 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8]([CH2:10]Br)[CH:7]=[CH:6][C:5]=1[N+:12]([O-:14])=[O:13].[NH:16]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].C(=O)([O-])[O-].[Cs+].[Cs+].O>CC(=O)CC.[Cl-].[Na+].O.[I-].[Li+].C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8]([CH2:10][N:16]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH:7]=[CH:6][C:5]=1[N+:12]([O-:14])=[O:13]

Participants

9

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 279800Di-tert-butyl IminodicarboxylateHCID 13399988Methyl 5-(bromomethyl)-2-nitrobenzoate

Product 1

HCID 687297825-(Di-tert-butoxycarbonylamino-methyl)-2-nitro-benzoic acid methyl esterYield 98.2%

Reagents, catalysts & solvents 4

HCID 66321Lithium iodideCatalystHCID 6569Methyl Ethyl KetoneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

A stirred mixture of 5-bromomethyl-2-nitro-benzoic acid methyl ester (50.5 g, 184 mmol), di-tert-butyl iminodicarboxylate (40.15 g, 185 mmol), cesium carbonate (123.1 g, 377.7 mmol), and lithium iodide (1.23 g, 9.21 mmol) in 2-butanone (556 mL) was heated to reflux in a 100° C. oil bath for 12 hours while stirred with a mechanical stirrer. The mixture was allowed to cool to room temperature. To the mixture, was added brine (300 mL), water (300 mL), and ethyl acetate (750 mL), and the mixture was stirred for 10 minutes. The suspension was filtered through a pad of Celite. The two layers were separated, and the organic layer was evaporated to a less volume. The aqueous layer was extracted with ethyl acetate (2×150 mL). The combined organic layers were washed with brine (500 mL), dried over magnesium sulfate while de-colored at the same time by charcoal at room temp with stirring for 30 minutes. The black mixture was filtered through a pad of Celite. The filtrate was evaporated to give 5-(di-tert-butoxycarbonylamino-methyl)-2-nitro-benzoic acid methyl ester as a brown oil (74.18 g, 98% yield). The product was used in the next step without further purification.

Workup

  1. temperaturewas heated
  2. temperatureto cool to room temperature
  3. stirringthe mixture was stirred for 10 minutes
  4. filtrationThe suspension was filtered through a pad of Celite
  5. customThe two layers were separated
  6. customthe organic layer was evaporated to a less volume
  7. extractionThe aqueous layer was extracted with ethyl acetate (2×150 mL)
  8. washThe combined organic layers were washed with brine (500 mL)
  9. dry with materialdried over magnesium sulfate while de-colored at the same time by charcoal at room temp
  10. stirringwith stirring for 30 minutes
  11. filtrationThe black mixture was filtered through a pad of Celite
  12. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-d9676e28c1ff485784b6e2d8d8527648
Source dataset
uspto-grants-2013_07
Patent number
US08492395B2

Reaction notes

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