Diethyl Ether → 5-(Tert-butoxycarbonylamino-methyl)-2-nitro-benzoic acid

HRID 509478Notes

Reaction equation

HRID 509478 reaction equation
C[O:2][C:3](=[O:22])[C:4]1[CH:9]=[C:8]([CH2:10][NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:7]=[CH:6][C:5]=1[N+:19]([O-:21])=[O:20].[OH-].[Li+].CCOCC>CO.O>[C:15]([O:14][C:12]([NH:11][CH2:10][C:8]1[CH:7]=[CH:6][C:5]([N+:19]([O-:21])=[O:20])=[C:4]([CH:9]=1)[C:3]([OH:22])=[O:2])=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 3939Lithium HydroxideHCID 19698365Methyl 5-tert-butoxycarbonylaminomethyl-2-nitrobenzoate

Product 1

HCID 666971495-(Tert-butoxycarbonylamino-methyl)-2-nitro-benzoic acidYield 41.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A mixture of 5-(tert-butoxycarbonylamino-methyl)-2-nitro-benzoic acid methyl ester (52.5 g, 169.3 mmol), lithium hydroxide (4.86 g, 203.1 mmol) in methanol (546 mL) and water (273 mL) was stirred with a mechanical stirrer at room temp overnight. The methanol was evaporated, and to the aqueous solution, was added 1 N HCl (270 mL) to form the precipitate. Ether (350 mL) was added, and the mixture was stirred at 0° C. for 2 hours. The mixture was evaporated. To the residue, was added water (500 mL). The aqueous layer was extracted with methylene chloride (3×100 mL). The combined organic layers were separated, dried over magnesium sulfate, and concentrated to give 5-(tert-butoxycarbonylamino-methyl)-2-nitro-benzoic acid as a brown oil (21.0 g, 41% yield). The product was used in the next step without further purification.

Workup

  1. customThe methanol was evaporated
  2. additionto the aqueous solution, was added 1 N HCl (270 mL)
  3. customto form the precipitate
  4. stirringthe mixture was stirred at 0° C. for 2 hours
  5. customThe mixture was evaporated
  6. additionTo the residue, was added water (500 mL)
  7. extractionThe aqueous layer was extracted with methylene chloride (3×100 mL)
  8. customThe combined organic layers were separated
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-b8c623897955435fb9f8cae57c405df2
Source dataset
uspto-grants-2015_08
Patent number
US09096573B2

Reaction notes

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