Sodium hydride → HCID 67485792, compound
Reaction equation
[CH3:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[H-].[Na+].Br[C:12]1[CH:13]=[C:14]([N+]([O-])=O)[C:15]([C:18]#[N:19])=[N:16][CH:17]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[SH:29]>CN(C=O)C>[CH3:1][C:2]1[C:7]([O:8][C:14]2[C:15]([C:18]#[N:19])=[N:16][CH:17]=[C:12]([S:29][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=3)[CH:13]=2)=[CH:6][CH:5]=[CH:4][N:3]=1Participants
Conditions
- Temperature
- 2 °C
Procedure
To 600 mL of DMF in a 4 neck 3000 mL round bottom flask equipped with an overhead stir mechanism under nitrogen was added 2-methylpyridin-3-ol (71.8 g, 658 mmol) and the reaction cooled to 2° C. 60% sodium hydride (26.3 g, 658 mmol) was added at such as rate that the internal temperature did not exceed 10° C. over a period of 30 minutes. The reaction was stirred while warming to ambient temperature for 1 hours. To the reaction was added 5-bromo-3-nitropicolinonitrile (150 g, 658 mmol) in a solution of 400 mL of DMF in two portions and the reaction held at ambient temperature for 1.5 hours. To the reaction at ambient temperature was added pyridine-2-thiol (73.1 g, 658 mmol) as a solid in portions and the reaction was stirred for 15 minutes to dissolve the material. The reaction was cooled to 3° C. and sodium hydride (26.3 g, 658 mmol) again was added in portions such that the internal temp did not go above 10° C. (35 minute addition time). The reaction was removed from the ice bath and warmed to ambient temperature while stirring for 12 hours. The reaction was diluted with 4 volumes (8 L) of brine. The mixture was stirred for 30 minutes, at which point solid formed. The solid was filtered off and filtrate extracted with MTBE (10 L total). The MTBE phase was concentrated in vacuo. The solid was combined with concentrated material and dissolved in ethyl acetate (3 L). The EtOAc was washed with brine (4×1 L), dried over MgSO4, filtered and concentrated in vacuo. The solid that formed was ground into a powder and dried in vacuo for 4 hours. The material was taken up in 30 mL of MTBE/10 g of product and the reaction was stirred for 30 minutes. The solid was filtered and dried in vacuo (2 hours). The solids were combined and dried for 3 hours in vacuo to yield 3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)picolinonitrile (181 g, 85%)
Workup
- stirringThe reaction was stirred
- temperaturewhile warming to ambient temperature for 1 hours
- waitthe reaction held at ambient temperature for 1.5 hours
- customTo the reaction at ambient temperature
- stirringthe reaction was stirred for 15 minutes
- dissolutionto dissolve the material
- temperatureThe reaction was cooled to 3° C.
- customdid not go above 10° C.
- addition(35 minute addition time)
- customThe reaction was removed from the ice bath
- temperaturewarmed to ambient temperature
- stirringwhile stirring for 12 hours
- additionThe reaction was diluted with 4 volumes (8 L) of brine
- stirringThe mixture was stirred for 30 minutes, at which point solid
- customformed
- filtrationThe solid was filtered off
- extractionfiltrate extracted with MTBE (10 L total)
- concentrationThe MTBE phase was concentrated in vacuo
- dissolutiondissolved in ethyl acetate (3 L)
- washThe EtOAc was washed with brine (4×1 L)
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe solid that formed
- customdried in vacuo for 4 hours
- stirringthe reaction was stirred for 30 minutes
- filtrationThe solid was filtered
- customdried in vacuo (2 hours)
- customdried for 3 hours in vacuo
Sources & evidence
- ORD record
- ord-0b731e0fee564f76b51824dc04b1afd3
- Source dataset
- uspto-grants-2012_07
- Patent number
- US08212045B2
Reaction notes
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