Acetic Acid → Ethyl 5-[bis(cyclopropylmethyl)amino]-2-chlorobenzoate

HRID 406401Notes

Reaction equation

HRID 406401 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:13])=[C:6]([CH:12]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8].[CH:14]1([CH:17]=O)[CH2:16][CH2:15]1.C(O)(=O)C.B.N1[CH:29]=[CH:28][CH:27]=[CH:26]C=1C>CO>[CH:14]1([CH2:17][N:1]([CH2:26][CH:27]2[CH2:29][CH2:28]2)[C:2]2[CH:3]=[CH:4][C:5]([Cl:13])=[C:6]([CH:12]=2)[C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 123114CyclopropanecarboxaldehydeHCID 13226857Ethyl 5-amino-2-chlorobenzoateHCID 16217944Borane;2-methylpyridine

Product 1

HCID 66618819Ethyl 5-[bis(cyclopropylmethyl)amino]-2-chlorobenzoate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To the mixture of ethyl 5-amino-2-chlorobenzoate, cyclopropanecarboxaldehyde (458 μl) and acetic acid (1.43 ml) dissolved in methanol (20 ml), α-picoline borane (804 mg) was added at ice cool temperature, and was stirred under nitrogen atmosphere overnight at room temperature. After the reaction mixture was concentrated under reduced pressure, sodium hydrogencarbonate aqueous solution was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography, and ethyl 2-chloro-5-(cyclopropylmethylamino)benzoate (881 mg) and ethyl 5-[bis(cyclopropylmethyl)amino]-2-chlorobenzoate (423 mg) were obtained.

Workup

  1. temperaturecool temperature
  2. concentrationAfter the reaction mixture was concentrated under reduced pressure, sodium hydrogencarbonate aqueous solution
  3. additionwas added to the residue
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography, and ethyl 2-chloro-5-(cyclopropylmethylamino)benzoate (881 mg)

Sources & evidence

ORD record
ord-e99f442c967e4504a62d699bd68558a7
Source dataset
uspto-grants-2014_06
Patent number
US08754100B2

Reaction notes

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