Ammonium Chloride → N-(2-cyanoethyl)-2,2-bisfluoromethyl-6-trifluoromethyl-2H-1-benzopyran-4-carbothioamide

HRID 1282435Notes

Reaction equation

HRID 1282435 reaction equation
Br[C:2]1[C:7]2[CH:8]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:10]=[CH:11][C:6]=2[O:5][C:4]([CH2:18][F:19])([CH2:16][F:17])[CH:3]=1.C([Li])CCC.[Cu]C#N.[C:28]([CH2:30][CH2:31][N:32]=[C:33]=[S:34])#[N:29].[Cl-].[NH4+]>C(OCC)C.O1CCCC1>[C:28]([CH2:30][CH2:31][NH:32][C:33]([C:2]1[C:7]2[CH:8]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:10]=[CH:11][C:6]=2[O:5][C:4]([CH2:18][F:19])([CH2:16][F:17])[CH:3]=1)=[S:34])#[N:29]

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 29349Isothiocyanic acid, 2-cyanoethyl esterHCID 184244094-bromo-2,2-bis(fluoromethyl)-6-trifluoromethyl-2H-1-benzopyranHCID 178418339ButyllithiumHCID 178418546HCID 178418546, compound

Product 1

HCID 18424394N-(2-cyanoethyl)-2,2-bisfluoromethyl-6-trifluoromethyl-2H-1-benzopyran-4-carbothioamideYield 7.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

An amount (103 mg) of 4-bromo-2,2-bis(fluoromethyl)-6-trifluoromethyl-2H-1-benzopyran was dissolved in diethyl ether (0.5 ml); to the solution, 1.68 M n-butyllithium (0.18 ml) was added at −10° C. under a nitrogen atmosphere. After stirring the reaction mixture for 10 minutes, copper(I) cyanide (27 mg) and tetrahydrofuran (0.6 ml) were added and the resulting mixture was stirred for 30 minutes at 0° C. Subsequently, a tetrahydrofuran solution (0.3 ml) of 2-cyanoethyl isothiocyanate (34 mg) was added and the mixture was stirred for 4 hours at 0° C. To the reaction mixture, a saturated aqueous solution of ammonium chloride was added, followed by extraction with diethyl ether; the resulting organic layer was washed with 2 N HCl, a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride, dried with anhydrous sodium sulfate and concentrated under reduced pressure; the resulting residue was subjected to silica gel column chromatography (eluent; dichloromethane/diethyl ether=10/1) to give the titled compound (8 mg), which was identical to the authentic sample.

Workup

  1. stirringthe resulting mixture was stirred for 30 minutes at 0° C
  2. stirringthe mixture was stirred for 4 hours at 0° C
  3. extractionfollowed by extraction with diethyl ether
  4. washthe resulting organic layer was washed with 2 N HCl
  5. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride, dried with anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5c40cc711cc64892b547433452b07683
Source dataset
uspto-grants-2002_09
Patent number
US06455708B1

Reaction notes

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