Acetic Acid → 5-Chloro-2-ethyl-3-[ethyl(oxan-4-yl)amino]benzoic acid

HRID 1616482Notes

Reaction equation

HRID 1616482 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:14][CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]([CH2:12][CH3:13])=[C:6]([CH:11]=1)[C:7]([O:9]C)=[O:8].[CH:21](=O)[CH3:22].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.O>[Cl:1][C:2]1[CH:3]=[C:4]([N:14]([CH2:21][CH3:22])[CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]([CH2:12][CH3:13])=[C:6]([CH:11]=1)[C:7]([OH:9])=[O:8]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 177Acetaldehyde2×HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 70872938Methyl 5-chloro-2-ethyl-3-[(oxan-4-yl)amino]benzoate

Product 1

HCID 708722245-Chloro-2-ethyl-3-[ethyl(oxan-4-yl)amino]benzoic acidYield 86.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

To a solution of methyl 5-chloro-2-ethyl-3-[(oxan-4-yl)amino]benzoate (350 mg, 1.18 mmol) in DCE (10 ml) at room temperature and under nitrogen was added acetaldehyde (0.66 ml, 11.75 mmol) followed by acetic acid (0.4 ml, 7.05 mmol). This solution was stirred for 5 minutes before the addition of sodium triacetoxyborohydride (2.49 g, 11.75 mmol) at room temperature. After stirring for 23 h further acetaldehyde (0.66 ml, 11.75 mmol) was added followed sodium triacetoxyborohydride (2.49 g, 11.75 mmol). After stirring for a further 3 hours deionized water (15 ml) was added and the mixture was neutralized with solid NaHCO3. The phases were separated and the aqueous layer was extracted with EtOAc (2×15 ml). The combined organic extracts were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by FCC (10 g silica, Isolute cartridge, gradient of eluents; 99:1 Heptane:EtOAc to 85:15 Heptane:EtOAc) to afford the title compound (317 mg) as a 2:1 mixture of methyl and ethyl esters that were used in the next stage.

Workup

  1. additionwas added
  2. additionwas added
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×15 ml)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by FCC (10 g silica, Isolute cartridge, gradient of eluents; 99:1 Heptane:EtOAc to 85:15 Heptane:EtOAc)

Sources & evidence

ORD record
ord-ec42b54547794e69b46a6adc3fe27128
Source dataset
uspto-grants-2014_07
Patent number
US08765732B2

Reaction notes

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