2-Amino-3-chlorobenzoic acid → 3-chloro-2-[3-(3-chloro-propyl)-ureido]-benzoic Acid

HRID 1266981Notes

Reaction equation

[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[Cl:12][CH2:13][CH2:14][CH2:15][N:16]=[C:17]=[O:18].[N-]=C=O>Cl>[Cl:11][C:10]1[C:2]([NH:1][C:17]([NH:16][CH2:15][CH2:14][CH2:13][Cl:12])=[O:18])=[C:3]([CH:7]=[CH:8][CH:9]=1)[C:4]([OH:6])=[O:5]

Participants

Conditions

Temperature: 0 °C

Procedure

A 250 mL round bottom flask is charged with 2-amino-3-chlorobenzoic acid (5.00 g, 29.1 mmol) and 100 mL of 5% aqueous KHCO3. The slurry is cooled to 0° C., and 3-chloropropylisocyanate (6.0 mL, 58 mmol) is added. The mixture is then allowed to warm to room temperature over 16 hours. HPLC analysis shows some starting material remaining, so the solution is recooled to 0° C. and an additional portion of the isocyanate (3.0 mL, 29 mmol) is added. After 2 hours, the solution is acidified with 1 N HCl (ca. 40 mL), and the resulting yellow solid is filtered, rinsing with 1 N HCl. The resulting solid (35.5 g) is recrystallized from 80 mL of hot ethanol, to provide the product as a white solid: 4.22 g, 14.5 mmol, 50% yield. M.p. 124.4-124.8° C. 1H NMR (CD3OD): 7.84 (d, J=8, 1H), 7.64 (d, J=8, 1H), 7.24 (t, J=8, 1H), 3.68 (t, J=7, 2H), 3.37 (t, J=6, 2H), 2.01 (m, 2H). MS (Cl): 289 (M−H, 100), 196 (M-ClCH2CH2CH2NH, 25)

Workup

temperatureto warm to room temperature over 16 hours
customis recooled to 0° C.
filtrationthe resulting yellow solid is filtered
washrinsing with 1 N HCl
customThe resulting solid (35.5 g) is recrystallized from 80 mL of hot ethanol

Sources & evidence

ORD record: ord-765ef128339d4122a638958cc6c92f29
Source dataset: uspto-grants-2003_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06552015B2

Reaction notes

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