Aniline → Benzoic acid, 4-[(phenylamino)methyl]-, methyl ester

HRID 1501043Notes

Reaction equation

HRID 1501043 reaction equation
[CH:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1)=O.[NH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[C:14]1([NH:13][CH2:1][C:3]2[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 6115AnilineHCID 15294Methyl 4-FormylbenzoateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 11579611Benzoic acid, 4-[(phenylamino)methyl]-, methyl esterYield 55.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

Methyl 4-formylbenzoate (1 g, 6 mmol) and aniline (837 mg, 9 mmol) were dissolved in methanol (30 mL). The mixture was heated to 50° C., and acetic acid (two or three drop) was added to the reaction mixture. The resultant mixture was stirred at 50° C. for 1 hour. After the mixture was cooled to room temperature, sodium cyanoborohydride (1.13 g, 18 mmol) was added. The mixture was stirred at room temperature for 18 hours. The reaction was quenched with water (10 mL) and the mixture was extracted with dichloromethane (10 mL×3). The combined organic phase was separated, dried by sodium sulfate and then filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=8:1) to give methyl 4-((phenylamino)methyl)benzoate (0.8 g, 55%). LRMS (M+H+) m/z: cald. 241.08. found 241. LRMS (M+H+) m/z: calcd 241.08. found 241. 1H NMR (300 MHz, CD3OD): δ 7.95 (dd, J=7.2 Hz, J=2.1 Hz, 2H), 7.44 (d, J=7.8 Hz, 2H), 7.05 (t, J=6.0 Hz, 2H), 6.60-6.56 (m, 3H), 4.37 (s, 2H), 3.86 (s, 3H).

Workup

  1. temperatureAfter the mixture was cooled to room temperature
  2. customThe reaction was quenched with water (10 mL)
  3. extractionthe mixture was extracted with dichloromethane (10 mL×3)
  4. customThe combined organic phase was separated
  5. dry with materialdried by sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customThe residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=8:1)

Sources & evidence

ORD record
ord-b8bdc8f9ec364f40a015f9bb5ccc8149
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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