Phosphoric Acid → Ethyl 2-(2-(((2-(benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)amino)ethoxy)-3-bromo-6-methyl-5-((methylsulfonyl)oxy)benzoate

HRID 577557Notes

Reaction equation

HRID 577557 reaction equation
[CH2:1]([O:8][C:9]1[C:14]([CH2:15][N:16](C(OC(C)(C)C)=O)[CH2:17][CH2:18][O:19][C:20]2[C:30]([Br:31])=[CH:29][C:28]([O:32][S:33]([CH3:36])(=[O:35])=[O:34])=[C:27]([CH3:37])[C:21]=2[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:13]([CH3:45])[CH:12]=[C:11]([CH3:46])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(=O)(O)(O)O>ClCCl>[CH2:1]([O:8][C:9]1[C:14]([CH2:15][NH:16][CH2:17][CH2:18][O:19][C:20]2[C:30]([Br:31])=[CH:29][C:28]([O:32][S:33]([CH3:36])(=[O:34])=[O:35])=[C:27]([CH3:37])[C:21]=2[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:13]([CH3:45])[CH:12]=[C:11]([CH3:46])[N:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 1004Phosphoric Acid2×HCID 86723783Ethyl 2-(2-(((2-(benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)(tert-butoxycarbonyl)amino)ethoxy)-3-bromo-6-methyl-5-((methylsulfonyl)oxy)benzoate

Product 1

HCID 86723784Ethyl 2-(2-(((2-(benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)amino)ethoxy)-3-bromo-6-methyl-5-((methylsulfonyl)oxy)benzoateYield 50.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of ethyl 2-(2-(((2-(benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)(tert-butoxycarbonyl)amino)ethoxy)-3-bromo-6-methyl-5-((methylsulfonyl)oxy)benzoate (116e, 0.58 g, 0.80 mmol) in dichloromethane (8 mL) was added 85% phosphoric acid (0.20 mL, 2.8 mmol). The mixture was stirred at room temperature for 2 hours then additional 85% phosphoric acid (0.20 mL, 2.8 mmol) was added and stirring was continued for 2 hours. The reaction was carefully quenched with saturated aqueous sodium bicarbonate (10 mL) and extracted with dichloromethane (2×15 mL). The combined organic layers were washed with brine (15 mL), dried over magnesium sulfate, concentrated under vacuum, and purified by column chromatography (20% EtOAc/Heptane) to give ethyl 2-(2-(((2-(benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)amino)ethoxy)-3-bromo-6-methyl-5-((methylsulfonyl)oxy)benzoate (116f, 0.25 g, 50% yield) as a clear sticky solid.

Workup

  1. stirringstirring
  2. waitwas continued for 2 hours
  3. customThe reaction was carefully quenched with saturated aqueous sodium bicarbonate (10 mL)
  4. extractionextracted with dichloromethane (2×15 mL)
  5. washThe combined organic layers were washed with brine (15 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under vacuum
  8. custompurified by column chromatography (20% EtOAc/Heptane)

Sources & evidence

ORD record
ord-0608b5bd9b9b4c7aad24c8f6ae0c9ab2
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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