2-Bromo-6-fluoroaniline → 1-(2-Bromo-6-fluorophenyl)-3-(2-methoxy-5-(trifluoromethyl)phenyl)urea

HRID 387181Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:4]=1[N:13]=[C:14]=[O:15].[Br:16][C:17]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:18]=1[NH2:19]>C(#N)C.C(OC(C)C)(C)C>[Br:16][C:17]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:18]=1[NH:19][C:14]([NH:13][C:4]1[CH:5]=[C:6]([C:9]([F:12])([F:11])[F:10])[CH:7]=[CH:8][C:3]=1[O:2][CH3:1])=[O:15]

Participants

Conditions

Temperature: 81 °C

Procedure

2-Methoxy-5-trifluoromethylphenyl isocyanate (1.19 kg) is fused at about 35° C. and dissolved in acetonitrile (4.2 l), then 2-bromo-6-fluoroaniline (870 g) is added and rinsed out with acetonitrile (380 ml). The resulting clear solution is stirred at 74-88° C. for 45 h, then concentrated in vacuo (200 mbar) at 50° C. to give a viscous magma (amount of distillate 4.4 l). This is diluted at room temperature with diisopropyl ether (1.5 l), filtered off with suction, washed with diisopropyl ether (1.15 l) and dried at 45° C. in the VDO using entraining nitrogen to constant mass (24 h). A total of 1.63 kg of N-(2-bromo-6-fluorophenyl)-N′-[2-methoxy-5-(trifluoromethyl)phenyl]urea is obtained as a solid, corresponding to 87.5% of theory.

Workup

customis fused at about 35° C.
washrinsed out with acetonitrile (380 ml)
concentrationconcentrated in vacuo (200 mbar) at 50° C.
customto give a viscous magma (amount of distillate 4.4 l)
filtrationfiltered off with suction
washwashed with diisopropyl ether (1.15 l)
customdried at 45° C. in the VDO
customto constant mass (24 h)

Sources & evidence

ORD record: ord-205c67d956684c8db8c57b7dd87c2709
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08372972B2

Reaction notes

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