Toluene → HCID 178492965, compound

HRID 1819269Notes

Reaction equation

HRID 1819269 reaction equation
[Cl-].[Cl:2][C:3]1[CH:8]=[CH:7][NH+:6]=[C:5]([CH2:9]Cl)[C:4]=1[O:11][CH3:12].[F:13][CH:14]([F:26])[O:15][C:16]1[CH:25]=[CH:24][C:19]2[NH:20][C:21]([SH:23])=[N:22][C:18]=2[CH:17]=1.C1(C)C=CC=CC=1.[OH-].[Na+]>O>[OH2:11].[F:26][CH:14]([F:13])[O:15][C:16]1[CH:25]=[CH:24][C:19]2[NH:20][C:21]([S:23][CH2:9][C:5]3[C:4]([O:11][CH3:12])=[C:3]([Cl:2])[CH:8]=[CH:7][N:6]=3)=[N:22][C:18]=2[CH:17]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 14798Sodium HydroxideHCID 685400364-Chloro-2-chloromethyl-3-methoxypyridinium chlorideHCID 178506406HCID 178506406, compound

Product 1

HCID 178492965HCID 178492965, compoundYield 4.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
60 °C

Procedure

At 55-65° C., a solution of 4-chloro-2-chloromethyl-3-methoxypyridinium chloride (10.0 kg, 43.8 mol) in water (20 L) was added over 2-3 h to a mixture of 5-difluoromethoxy-1H-benzimidazole-2-thiol (8.84 kg, 40.9 mol), toluene (43 L), water (21 L) and 40% aqueous NaOH (10.3 kg, 103 mol). Stirring at 60° C. was continued for 2-3 h before the reaction mixture was cooled to 10-15° C. The precipitate was centrifuged off, washed with toluene (16 L) and re-pulped in water (122 L). Centrifugation followed by an aqueous rinse (32 L) and drying at 35° C. in vacuo gave 5-difluoromethoxy-2-[(4-chloro-3-methoxy-2-pyridinyl)methylthio]-1H-benzimidazole mono hydrate (KF=4.6%) as an off-white solid (m. p. 95-99° C.); yield 14.2 kg (92%).

Workup

  1. temperaturewas cooled to 10-15° C
  2. washwashed with toluene (16 L) and re-pulped in water (122 L)
  3. washan aqueous rinse (32 L)
  4. customdrying at 35° C. in vacuo

Sources & evidence

ORD record
ord-08d8d35c1be744689a295ad462ecacd8
Source dataset
uspto-grants-2009_10
Patent number
US07601737B2

Reaction notes

Loading…