Potassium Iodide → Methyl 2-(3-tert-butoxycarbonylaminopropoxy)-4-methoxybenzoate

HRID 644271Notes

Reaction equation

HRID 644271 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([OH:13])[C:6](=[CH:11][CH:12]=1)[C:7]([O:9][CH3:10])=[O:8].[C:14]([O:18][C:19]([NH:21][CH2:22][CH2:23][CH2:24]Br)=[O:20])([CH3:17])([CH3:16])[CH3:15].[I-].[K+]>CN(C)C=O.O>[C:14]([O:18][C:19]([NH:21][CH2:22][CH2:23][CH2:24][O:13][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[CH:12]=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8])=[O:20])([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 3

HCID 4875Potassium IodideHCID 79523Methyl 4-methoxysalicylateHCID 4460490tert-butyl N-(3-bromopropyl)carbamate

Product 1

HCID 68534059Methyl 2-(3-tert-butoxycarbonylaminopropoxy)-4-methoxybenzoateYield 93.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 4-methoxysalicylate (11.48 g, 63 mmol) in dimethylformamide (30 mL) was added solid K2 CO3 (13.06 g, 94.5 mmol), 1-tert-butoxycarbonylamino-3-bromopropane (22.5 g, 94.5 mmol), and freshly ground potassium iodide (1.5 g). The resulting slurry was placed under a nitrogen atmosphere and stirred for 2.5 days. The slurry was diluted with water (250 mL), washed with 1 N NaOH (2×250 mL), water (250 mL), and brine (250 mL), then dried over sodium sulfate and concentrated in vacuo. The crude mixture was purified on a preparative HPLC chromatograph using two silica columns and a hexanes through 1:1 hexanes:EtOAc gradient to provide methyl 2-(3-tert-butoxycarbonylaminopropoxy)-4-methoxybenzoate (19.93 g, 93.3%) as a colorless oil.

Workup

  1. washwashed with 1 N NaOH (2×250 mL), water (250 mL), and brine (250 mL)
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe crude mixture was purified on a preparative HPLC chromatograph

Sources & evidence

ORD record
ord-d1c520cada8b4d359ab555a6c09abf7d
Source dataset
uspto-grants-2010_04
Patent number
US07700628B2

Reaction notes

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