Methyl 4-aminobenzoate → Methyl 4-[[(5-methyl-2-thienyl)methyl]amino]benzoate

HRID 1593980Notes

Reaction equation

HRID 1593980 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.[CH3:12][C:13]1[S:17][C:16]([CH:18]=O)=[CH:15][CH:14]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[CH3:9][O:8][C:6](=[O:7])[C:5]1[CH:4]=[CH:3][C:2]([NH:1][CH2:18][C:16]2[S:17][C:13]([CH3:12])=[CH:14][CH:15]=2)=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 12082Methyl 4-aminobenzoateHCID 616635-Methyl-2-thiophenecarboxaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 43139107Methyl 4-[[(5-methyl-2-thienyl)methyl]amino]benzoateYield 90.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 200 mg (1.32 mmol) methyl 4-aminobenzoate and 167 mg (1.32 mmol) 5-methyl-2-thiophenecarboxaldehyde dissolved in 8 mL dichloromethane was added 420 mg (1.98 mmol) sodium triacetoxyborohydride. The mixture was stirred at room temperature overnight, then partitioned between ethyl acetate and water, dried over magnesium sulfate and concentrated. Column chromatography, eluting with 20% ethyl acetate/hexane, provided 316 mg (1.2 mmol) of 4-[(5-Methyl-thiophen-2-ylmethyl)-amino]-benzoic acid methyl ester. This product was then dissolved in 10 mL methanol and treated with 127 mg (3.0 mmol) of lithium hydroxide dissolved in 5 mL water. The mixture was stirred at room temperature overnight, then partitioned between ethyl acetate and 1 N HCl, dried over magnesium sulfate and concentrated to provide 276 mg (92% yield) of 4-[(5-methyl-thiophen-2-ylmethyl)-amino]-benzoic acid (used in preparation of compound 64 of Table 1) as a pale yellow solid.

Workup

  1. custompartitioned between ethyl acetate and water
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated
  4. washColumn chromatography, eluting with 20% ethyl acetate/hexane

Sources & evidence

ORD record
ord-61f150a06ba742ddbaf71b9c2fbaeb8a
Source dataset
uspto-grants-2007_11
Patent number
US07300934B2

Reaction notes

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