Acetic Acid → methyl 5-bromo-2-methyl-3-((tetrahydro-2H-pyran-4-yl)amino)benzoate

HRID 1530251Notes

Reaction equation

HRID 1530251 reaction equation
[NH2:1][C:2]1[C:3]([CH3:13])=[C:4]([CH:9]=[C:10]([Br:12])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:14]([OH:17])(=O)[CH3:15].C(O[BH-](O[C:28](=O)[CH3:29])OC(=O)C)(=O)C.[Na+].[C:32](=O)(O)[O-].[Na+]>ClC(Cl)C>[Br:12][C:10]1[CH:11]=[C:2]([NH:1][CH:32]2[CH2:15][CH2:14][O:17][CH2:29][CH2:28]2)[C:3]([CH3:13])=[C:4]([CH:9]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 24729181Methyl 3-Amino-5-bromo-2-methylbenzoate

Product 1

HCID 70872676methyl 5-bromo-2-methyl-3-((tetrahydro-2H-pyran-4-yl)amino)benzoateYield 69%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a stirred solution of methyl 3-amino-5-bromo-2-methylbenzoate (15 g, 61.5 mmol) and dihydro-2H-pyran-4(3)-one (9.2 g, 92 mmol) in dichloroethane (300 mL) was added acetic acid (22 g, 369 mmol) and the reaction mixture stirred at room temperature for 15 minutes, upon which the reaction mixture was cooled to 0° C. and sodium triacetoxyborohydride (39 g, 183.96 mmol) was added. The reaction mixture was stirred overnight at room temperature. Aqueous sodium bicarbonate was then added to the reaction mixture adjusting the pH to 7-8. The organic phase was separated and the aqueous phase extracted with ethyl acetate. The combined extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (100-200 mesh silica gel) eluting with ethyl acetate: hexane to afford methyl 5-bromo-2-methyl-3-((tetrahydro-2H-pyran-4-yl)amino)benzoate as an off-white solid (14 g, 69%).

Workup

  1. temperaturewas cooled to 0° C.
  2. stirringThe reaction mixture was stirred overnight at room temperature
  3. customThe organic phase was separated
  4. extractionthe aqueous phase extracted with ethyl acetate
  5. dry with materialThe combined extracts were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by column chromatography (100-200 mesh silica gel)
  9. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-bbe0b10d30174187b5b33d8a5119a000
Source dataset
uspto-grants-2015_07
Patent number
US09090562B2

Reaction notes

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