Thiophosgene → 5-Chloro-2-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-isothiocyanato-2-phenylethyl)pyridine

HRID 1993606Notes

Reaction equation

HRID 1993606 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([F:27])[CH:18]=2)([NH2:16])[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1.C([O-])(O)=O.[Na+].[C:33](Cl)(Cl)=[S:34]>C(Cl)(Cl)Cl.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:24])[F:25])[CH:20]=[C:19]([F:27])[CH:18]=2)([N:16]=[C:33]=[S:34])[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 10040ThiophosgeneHCID 516892Sodium BicarbonateHCID 591345731-(5-Chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine

Product 1

HCID 866129665-Chloro-2-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-isothiocyanato-2-phenylethyl)pyridineYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6212ChloroformSolvent2×

Procedure

1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine (0.132 g, 0.335 mmol) in chloroform (1 mL) was added H2O (1 mL) and NaHCO3 (84 mg, 1.01 mmol). To this vigorously stirred mixture was added thiophosgene (38.3 μl, 0.502 mmol) dropwise. The reaction was stirred at room temperature for 2 hours and diluted with CHCl3 and H2O. The organic layer was separated and washed with brine, dried over MgSO4 and concentrated. The crude mixture was purified by silica gel ISCO chromatography (12 g column) using hexanes/EtOAc (0-30% over 20 min) to give 5-chloro-2-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-isothiocyanato-2-phenylethyl)pyridine as a yellow oil (73 mg, 50% yield). LCMS: 4.3 min [M+1] 437.1 (4 min gradient, MeOH/H2O 0.1% TFA); 1H NMR (400 MHz, CDCl3) δ ppm 3.72 (d, J=13.69 Hz, 2H), 4.07 (d, J=13.45 Hz, 2H), 6.89 (dd, J=7.83, 1.47 Hz, 3H), 7.16-7.22 (m, 5H), 7.24 (d, J=1.47 Hz, 1H), 7.37 (dt, J=4.22, 2.17 Hz, 2H), 7.40 (t, J=1.96 Hz, 1H), 7.52 (s, 2H), 7.66 (dd, J=8.31, 2.45 Hz, 2H), 8.65 (d, J=1.96 Hz, 2H).

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe crude mixture was purified by silica gel ISCO chromatography (12 g column)
  6. customhexanes/EtOAc (0-30% over 20 min)

Sources & evidence

ORD record
ord-0020ae78760943e08c04986670319fd0
Source dataset
uspto-grants-2010_01
Patent number
US07652023B2

Reaction notes

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