Hydrochloric Acid → 4-(8-Oxo-6-thioxo-5-(4-methylphenyl)-5,7-diazaspiro[3.4]oct-7-yl)-2-trifluoromethylbenzonitrile

HRID 1927328Notes

Reaction equation

HRID 1927328 reaction equation
[N:1]([C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[C:6]([C:12]([F:15])([F:14])[F:13])[CH:5]=1)=[C:2]=[S:3].[CH3:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24]2([C:28]#N)[CH2:27][CH2:26][CH2:25]2)=[CH:19][CH:18]=1.C[OH:31].Cl>CN(C=O)C.O>[O:31]=[C:28]1[C:24]2([CH2:27][CH2:26][CH2:25]2)[N:23]([C:20]2[CH:21]=[CH:22][C:17]([CH3:16])=[CH:18][CH:19]=2)[C:2](=[S:3])[N:1]1[C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[C:6]([C:12]([F:13])([F:15])[F:14])[CH:5]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 116155404-Isothiocyanato-2-(trifluoromethyl)benzonitrileHCID 609877761-(4-Methylphenyl)aminocyclobutanenitrile

Product 1

HCID 159527824-(8-Oxo-6-thioxo-5-(4-methylphenyl)-5,7-diazaspiro[3.4]oct-7-yl)-2-trifluoromethylbenzonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 1a (0.912 g, 4 mmol) and 7a (0.558 g, 3 mmol) in dry DMF (0.5 ml) was stirred at room temperature for 24 h. To this mixture were added methanol (30 ml) and HCl aq. 2N (6 ml). The second mixture was refluxed for 6 h. After being cooled to room temperature, the reaction mixture was poured into cold water (50 ml) and extracted with ethyl acetate (60 ml). The organic layer was dried over MgSO4, concentrated and chromatographed (dichloromethane) to yield 4-(8-oxo-6-thioxo-5-(4-methylphenyl)-5,7-diazaspiro[3.4]oct-7-yl)-2-trifluoromethylbenzonitrile, 7c (0.959 g, 2.31 mmol, 77%) as a white powder.

Workup

  1. temperatureThe second mixture was refluxed for 6 h
  2. temperatureAfter being cooled to room temperature
  3. extractionextracted with ethyl acetate (60 ml)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customchromatographed (dichloromethane)

Sources & evidence

ORD record
ord-589619d4f5d04f71bf563af567aa38fe
Source dataset
uspto-grants-2012_05
Patent number
US08183274B2

Reaction notes

Loading…