1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-amino-3-chloro-N-methylbenzamide

HRID 529669Notes

Reaction equation

[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][C:3]=1[Cl:11].C[CH2:13][N:14]=C=NCCCN(C)C.Cl.CN.C(=O)(O)[O-].[Na+]>CN(C=O)C>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:14][CH3:13])=[O:7])=[CH:4][C:3]=1[Cl:11]

Participants

Conditions

Temperature: 25 °C

Procedure

The solution of 4-amino-3-chlorobenzoic acid (1 equiv), EDCI (1.2 equiv), methylamine hydrochloride (1.2 equiv) in DMF (1.5 M) was added sodium bicarbonate (1 equiv). The reaction was stirred at 25° C. for 15 h. The reaction mixture was quenched with saturated aqueous sodium chloride and then extracted with ethyl acetate. The organic phase was combined and washed with saturated aqueous sodium chloride. The organic layer was dried (anhydrous magnesium sulfate), filtered, and concentrated. The crude product was purified by silica gel column chromatography (0-90% ethyl acetate (with 10% 1N ammonia in methanol) in hexane). Concentration of the desired fractions afforded the title compound (89% yield) as colorless oil; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.67 (d, J=4.29 Hz, 3 H) 5.81 (s, 2 H) 6.72 (d, J=8.59 Hz, 1 H) 7.49 (dd, J=8.39, 2.15 Hz, 1 H) 7.67 (d, J=1.95 Hz, 1 H) 8.08 (d, J=4.29 Hz, 1 H); MS (ESI) m/z 185.0 [M+1]+.

Workup

customThe reaction mixture was quenched with saturated aqueous sodium chloride
extractionextracted with ethyl acetate
washwashed with saturated aqueous sodium chloride
dry with materialThe organic layer was dried (anhydrous magnesium sulfate)
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by silica gel column chromatography (0-90% ethyl acetate (with 10% 1N ammonia in methanol) in hexane)

Sources & evidence

ORD record: ord-f02361750d1742a29db0bbdc2b82457a
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346812B2

Reaction notes

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