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

HRID 1959220Notes

Reaction equation

HRID 1959220 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:13][CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[CH:20](=O)[CH3:21].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClC(Cl)C>[Br:1][C:2]1[CH:3]=[C:4]([N:13]([CH2:20][CH3:21])[CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 177AcetaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 70872676methyl 5-bromo-2-methyl-3-((tetrahydro-2H-pyran-4-yl)amino)benzoate

Product 1

HCID 70872485methyl 5-bromo-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoateYield 93%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a stirred solution of methyl 5-bromo-2-methyl-3-((tetrahydro-2H-pyran-4-yl)amino)benzoate (14 g, 42.7 mmol) in dichloroethane (150 mL) was added acetaldehyde (3.75 g, 85.2 mmol) and acetic acid (15.3 g, 256 mmol). The resulting reaction mixture was stirred at room temperature for 15 minutes. The mixture was cooled to 0° C. and sodium triacetoxyborohydride (27 g, 128 mmol) was added. The reaction mixture was stirred at room temperature for 3 hours. Upon completion of the reaction as determined by TLC, aqueous sodium bicarbonate solution was added to the reaction mixture until a pH 7-8 was obtained, the organic phase was separated and the aqueous phase was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude compound was purified by column chromatography (100-200 mesh silica gel) eluting with ethyl acetate:hexane to afford the desired compound as a viscous liquid (14 g, 93%). 1H NMR (DMSO-d6, 400 MHz) δ 7.62 (s, 1H), 7.52 (s, 1H), 3.80 (bs, 5H), 3.31 (t, 2H), 2.97-3.05 (m, 2H), 2.87-2.96 (m, 1H), 2.38 (s, 3H), 1.52-1.61 (m, 2H), 1.37-1.50 (m, 2H), 0.87 (t, 3H, J=6.8 Hz).

Workup

  1. customThe resulting reaction mixture
  2. temperatureThe mixture was cooled to 0° C.
  3. stirringThe reaction mixture was stirred at room temperature for 3 hours
  4. customUpon completion of the reaction
  5. additionwas added to the reaction mixture until a pH 7-8
  6. customwas obtained
  7. customthe organic phase was separated
  8. extractionthe aqueous phase was extracted with ethyl acetate
  9. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe crude compound was purified by column chromatography (100-200 mesh silica gel)
  13. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-004492bd50aa42dc9be0c35f0ec52625
Source dataset
uspto-grants-2013_04
Patent number
US08410088B2

Reaction notes

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