Potassium thiocyanate → HCID 178448625, compound

HRID 2410265Notes

Reaction equation

HRID 2410265 reaction equation
[S-:1][C:2]#[N:3].[K+].[F:5][C:6]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][C:7]=1[C:8]([Cl:10])=[O:9].[CH2:19]([NH:23][C:24]1[C:25](Cl)=[N:26][CH:27]=[CH:28][CH:29]=1)[CH2:20][CH2:21][CH3:22]>O1CCCC1>[ClH:10].[CH2:19]([N:23]1[C:24]2[C:25](=[N:26][CH:27]=[CH:28][CH:29]=2)[S:1]/[C:2]/1=[N:3]\[C:8](=[O:9])[C:7]1[CH:11]=[C:12]([C:15]([F:18])([F:17])[F:16])[CH:13]=[CH:14][C:6]=1[F:5])[CH2:20][CH2:21][CH3:22]

Participants

5

Reactant 3

HCID 516872Potassium thiocyanateHCID 27348802-Fluoro-5-(trifluoromethyl)benzoyl ChlorideHCID 43690093N-Butyl-2-chloropyridin-3-amine

Product 1

HCID 178448625HCID 178448625, compoundYield 48.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a three-necked flask were charged potassium thiocyanate (5.0 g, 50.4 mmol), and tetrahydrofuran (110 mL). 2-Fluoro-5-(trifluoromethyl)benzoyl chloride (10.39 g, 41.7 mmol) was added into the flask slowly at room temperature. The reaction mixture was stirred at room temperature for 3 hours or until less than 1% of the acid chloride remains. The reaction mixture was filtered to remove potassium chloride by-product, and rinsed with tetrahydrofuran (10 mL). The combined solution of 2-fluoro-5-(trifluoromethyl)benzoyl isothiocyanate was charged back to the three-necked flask, followed by addition of N-butyl-2-chloropyridin-3-amine (6.91 g, 37.4 mmol) and tetrahydrofuran (100 mL). The reaction mixture was heated to approximately 50° C., and stirred vigorously for 2 days. The product suspension was then cooled to room temperature, and the product collected by filtration. The wet cake was washed with tetrahydrofuran (50 mL), and dried under vacuum at 50° C. to give the desired product (7.83 g, 48% isolated yield). MS-ESI: 398 (M+1); 1H-NMR (DMSO-d6) δ 0.96 (3H, t, J=7.4 Hz), 1.42 (2H, m), 1.81 (2H, m), 4.51 (2H, t, J=7.6 Hz), 7.53-7.64 (2H, m), 7.97-8.05 (1H, m), 8.21 (1H, dd, J=8.3, 1.2 Hz), 8.46 (1H, dd, J=6.7, 2.3 Hz), 8.52 (1H, dd, J=4.7, 1.2 Hz).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customto remove potassium chloride by-product
  3. washrinsed with tetrahydrofuran (10 mL)
  4. additionThe combined solution of 2-fluoro-5-(trifluoromethyl)benzoyl isothiocyanate was charged back to the three-necked flask
  5. temperatureThe product suspension was then cooled to room temperature
  6. filtrationthe product collected by filtration
  7. washThe wet cake was washed with tetrahydrofuran (50 mL)
  8. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-c3faeb9945414044946667715596e477
Source dataset
uspto-grants-2014_08
Patent number
US08816086B2

Reaction notes

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