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

HRID 2410223Notes

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-e7ab9be4e29b437aab69907b3518eb4b
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08816075B2

Reaction notes

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