Ammonia → 2-Amino-3-methoxybenzamide

HRID 625770Notes

Reaction equation

HRID 625770 reaction equation
[NH2:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].CC[N:15](C(C)C)C(C)C.N.CO.CCN=C=NCCCN(C)C.ON1C2C=CC=CC=2N=N1>CN(C=O)C.O>[NH2:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH2:15])=[O:5]

Participants

9

Reactant 6

HCID 222AmmoniaHCID 887MethanolHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2557202-Amino-3-methoxybenzoic acid

Product 1

HCID 185365712-Amino-3-methoxybenzamideYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To 2-amino-3-methoxybenzoic acid (8.11 g, 48.52 mmol) in DMF (150 mL) at rt were added DIEA (13.2 mL, 58.22 mmol), 2 N ammonia in MeOH (33.96 mL, 67.92 mmol), EDCI (11.16 g, 58.22 mmol), and 1-hydroxybenzotriazole (7.87 g, 58.22 mmol). The solution was stirred at rt under argon. After 20 h the solution was diluted with water and extracted ten times with EtOAc. The EtOAc volume was reduced and washed with brine. The EtOAc fraction was concentrated and diluted with diethyl ether. The resulting tan solid was collected and dried in vacuo to give 2-amino-3-methoxybenzamide (6.08 g, 76%). 1H NMR (300 MHz, DMSO-d6) δ 3.79 (s, 3H), 6.26 (bs, 2H), 6.48 (m, 1H), 6.88 (d, J=7.9 hz, 1H), 7.12 (bs, 1H), 7.19 (dd, J=8.2, 1.0 Hz, 1H), 7.70 (bs, 1H) LC-MS (ESI) m/z 167 (M+H)+.

Workup

  1. extractionextracted ten times with EtOAc
  2. washwashed with brine
  3. concentrationThe EtOAc fraction was concentrated
  4. additiondiluted with diethyl ether
  5. customThe resulting tan solid was collected
  6. customdried in vacuo

Sources & evidence

ORD record
ord-d416e5fda2cf4ba5a057f59ceb2503e0
Source dataset
uspto-grants-2016_04
Patent number
US09308207B2

Reaction notes

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