Ammonia → 4-{[(tert-Butoxycarbonyl)amino]methyl}-3-chlorobenzoic acid

HRID 432583Notes

Reaction equation

HRID 432583 reaction equation
[NH3:1].Br[CH2:3][C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10]C)=[O:9])=[CH:6][C:5]=1[Cl:14].[O:15](C(OC(C)(C)C)=O)[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=O.[OH-].[Na+]>C(O)C.O.O1CCOCC1>[C:19]([O:18][C:16]([NH:1][CH2:3][C:4]1[CH:13]=[CH:12][C:7]([C:8]([OH:10])=[O:9])=[CH:6][C:5]=1[Cl:14])=[O:15])([CH3:22])([CH3:21])[CH3:20]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 14798Sodium HydroxideHCID 90495Di-tert-butyl dicarbonateHCID 22027761Methyl 4-(bromomethyl)-3-chlorobenzoate

Product 1

HCID 220277744-{[(tert-Butoxycarbonyl)amino]methyl}-3-chlorobenzoic acid

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a saturated solution of ammonia in ethanol (170 ml) was added methyl 4-bromomethyl-3-chlorobenzoate from Example A1 (5.5 g, 20.9 mmol). The mixture was stirred at room temperature for 1 h and then concentrated in vacuo. The residue was triturated with diethyl ether and the resultant white crystals were filtered off and washed with more diethyl ether. To a solution of this solid in water (100 ml) were added solutions of (BOC)2O (5.0 g, 23.0 mmol) in dioxan (100 ml) and sodium hydroxide (1.86 g, 46.0 mmol) in water (100 ml). The mixture was stirred at room temperature for 18 h and then concentrated in vacuo. The aqueous residue was acidified with citric acid and extracted with chloroform/IPA. The organic layer was washed with water, dried over MgSO4, and concentrated in vacuo to give a white solid; yield 2.8 g (67%).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was triturated with diethyl ether
  3. filtrationthe resultant white crystals were filtered off
  4. washwashed with more diethyl ether
  5. stirringThe mixture was stirred at room temperature for 18 h
  6. concentrationconcentrated in vacuo
  7. extractionextracted with chloroform/IPA
  8. washThe organic layer was washed with water
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customto give a white solid

Sources & evidence

ORD record
ord-7dc800cb4e704341a76d42a433e113e1
Source dataset
uspto-grants-2003_12
Patent number
US06664249B1

Reaction notes

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