4-Bromo-2-chloroaniline → 4-(4-Bromo-2-chlorophenylamino)-6-chloronicotinic acid hydrochloride salt

HRID 917020Notes

Reaction equation

HRID 917020 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Br:11][C:12]1[CH:17]=[CH:16][C:15]([NH2:18])=[C:14]([Cl:19])[CH:13]=1.Cl[C:21]1[C:26]([C:27]([OH:29])=[O:28])=[CH:25][N:24]=[C:23]([Cl:30])[CH:22]=1>C1COCC1>[ClH:19].[Br:11][C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:21]2[C:26]([C:27]([OH:29])=[O:28])=[CH:25][N:24]=[C:23]([Cl:30])[CH:22]=2)=[C:14]([Cl:19])[CH:13]=1

Participants

5

Reactant 3

HCID 6101694-Bromo-2-chloroanilineHCID 8171584,6-Dichloronicotinic acidHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 865967774-(4-Bromo-2-chlorophenylamino)-6-chloronicotinic acid hydrochloride salt

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

LiHMDS (261 mL of a 1 M solution in hexanes) was added dropwise over 30 minutes to a solution of 4-bromo-2-chlorophenylamine (35.0 g, 172 mmol) in THF (80 mL) at −78° C. After 1 hour, 4,6-dichloronicotinic acid (23) (15.7 g, 81.7 mmol) was added dropwise over 30 minutes. The reaction mixture was slowly warmed to room temperature and stirred 16 hours. The reaction mixture was quenched with water, diluted with EtOAc and acidified with 1 N HCl. The resulting precipitate was isolated by filtration and washed with EtOAc. The solids were twice concentrated from toluene, triturated with CH2Cl2 and collected by filtration. The solids were further concentrated from toluene (3×) followed by drying in vacuo to give the desired product (24) containing a small amount of water (36.0 g).

Workup

  1. customThe reaction mixture was quenched with water
  2. additiondiluted with EtOAc
  3. customThe resulting precipitate was isolated by filtration
  4. washwashed with EtOAc
  5. concentrationThe solids were twice concentrated from toluene
  6. customtriturated with CH2Cl2
  7. filtrationcollected by filtration
  8. concentrationThe solids were further concentrated from toluene (3×)
  9. customby drying in vacuo

Sources & evidence

ORD record
ord-2b7104c059d94325b5de9a8139ba3472
Source dataset
uspto-grants-2007_09
Patent number
US07271178B2

Reaction notes

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