Potassium thiocyanate → HCID 178448622, compound

HRID 2410263Notes

Reaction equation

HRID 2410263 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[CH:25]=[N:26][CH:27]=[CH:28][C:29]=1Cl)[CH2:20][CH2:21][CH3:22]>O1CCCC1>[ClH:10].[CH2:19]([N:23]1[C:24]2[CH:25]=[N:26][CH:27]=[CH:28][C: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 54578954HCID 54578954, compound2×

Product 1

HCID 178448622HCID 178448622, compoundYield 93.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a three-necked flask were charged potassium thiocyanate (200.0 g, 2.03 mol), and tetrahydrofuran (6.78 L). 2-Fluoro-5-(trifluoromethyl)benzoyl chloride (471.0 g, 2.07 mol) was added into the flask slowly at room temperature. The reaction mixture was stirred at room temperature for 5 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 (about 0.5 L). The combined solution of 2-fluoro-5-(trifluoromethyl)benzoyl isothiocyanate was charged back to the three-necked flask, followed by addition of N-butyl-4-chloropyridin-3-amine (266.0 g, 1.44 mol). The reaction mixture was heated to approximately 50° C., and stirred vigorously overnight or until less than 1% of N-butyl-4-chloropyridin-3-amine remains. The product suspension was then cooled to room temperature, and the product collected by filtration. The wet cake was washed with tetrahydrofuran (1.0 L), and dried under vacuum at 60° C. to give the desired product (584.0 g, 93% isolated yield). MS-ESI: 398 (M+1); 1H-NMR (CDCl3-DMSO-d6) δ 0.96 (3H, t, J=7.4 Hz), 1.45 (2H, m), 1.84 (2H, m), 4.58 (2H, d, J=7.6 Hz), 7.49 (1H, t, J=9.0 Hz), 7.92 (1H, m), 8.42 (1H, d, J=5.8 Hz), 8.46 (1H, dd, J=6.6, 2.5 Hz), 8.65 (1H, d, J=6.6 Hz), 9.37 (1H, s); 13-NMR (CDCl3-DMSO-d6) δ 13.50, 19.47, 29.12, 46.08, 118.07 (d, J=23 Hz), 119.70, 122.90 (q, J=269 Hz, CF3), 123.96 (d, J=10 Hz), 124.84 (q, J=33 Hz, C—CF3), 128.21, 128.78, 130.70, 134.50, 137.03, 141.20, 162.78 (d, J=262 Hz, C—F), 165.79, 170.06 (d, J=4.0 Hz).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customto remove potassium chloride by-product
  3. washrinsed with tetrahydrofuran (about 0.5 L)
  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 (1.0 L)
  8. customdried under vacuum at 60° C.

Sources & evidence

ORD record
ord-4d3ca5444a02481db156e4628e7eacff
Source dataset
uspto-grants-2014_08
Patent number
US08816086B2

Reaction notes

Loading…