Dimethyl Sulfoxide → 1-(3,4-dichlorophenyl)-4-oxocyclohexanecarbonitrile

HRID 333291Notes

Reaction equation

HRID 333291 reaction equation
[C:1]([C:3]1([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=2)[CH2:8][CH:7](C(OC)=O)[C:6](=[O:13])[CH2:5][CH2:4]1)#[N:2].CS(C)=O.CCOC(C)=O.CCCCCCC>[Cl-].[Na+].O.O>[Cl:21][C:16]1[CH:15]=[C:14]([C:3]2([C:1]#[N:2])[CH2:4][CH2:5][C:6](=[O:13])[CH2:7][CH2:8]2)[CH:19]=[CH:18][C:17]=1[Cl:20]

Participants

6

Reactant 3

HCID 679Dimethyl SulfoxideHCID 12595532HCID 12595532, compoundHCID 21899848Ethylacetate heptane

Product 1

HCID 35255341-(3,4-dichlorophenyl)-4-oxocyclohexanecarbonitrileYield 109.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
135 °C

Procedure

To 12-L, four-neck flask equipped with a temperature probe, reflux condenser and overhead stirrer was charged with methyl 5-cyano-5-(3,4-dichlorophenyl)-2-oxocyclohexanecarboxylate (424 g, crude, 350 g theoretical, 1.07 mol), brine (500 mL) and DMSO (3.4 L). The mixture was heated to 135° C. and stirred for 12 h. The progress of the reaction was monitored by TLC (4:6 EtOAc/Heptane; stained using Hanessian solution). The reaction mixture was cooled to room temperature and combined with the crude mixture from a previous 145 g batch reaction, diluted with water (6 L), extracted with MTBE (6 L), and then EtOAc/MTBE (3:5, 8 L). The organics were combined and washed with brine (4×2.5 L), dried over MgSO4, filtered and concentrated under reduced pressure at 40-45° C. to afford a residue which was triturated with heptane/MTBE (1:1, 1.2 L). The resulting slurry was stirred for 0.5 h, filtered and dried under high vacuum for 2 h to afford the title compound [313 g, 77% over 2 steps, 100% (AUC) by GC] as an off-white solid. 1H NMR (DMSO-d6, 300 MHz): δ 7.9 (d, 1H), 7.75 (dd, 1H), 7.6 (dd, 1H), 2.8-2.5 (m, 2H), 2.48-2.3 (m, 6H).

Workup

  1. temperaturereflux condenser and overhead stirrer
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted with MTBE (6 L)
  4. washwashed with brine (4×2.5 L)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure at 40-45° C.
  8. customto afford a residue which
  9. customwas triturated with heptane/MTBE (1:1, 1.2 L)
  10. stirringThe resulting slurry was stirred for 0.5 h
  11. filtrationfiltered
  12. customdried under high vacuum for 2 h

Sources & evidence

ORD record
ord-90af66884f1e42ef8f002fe65b4f46bc
Source dataset
uspto-grants-2014_11
Patent number
US08877975B2

Reaction notes

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