Hydrochloric Acid → N-(1,1-Dimethyl-2-methylthioethyl)-N'-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]phthalamide

HRID 2358866Notes

Reaction equation

HRID 2358866 reaction equation
CC(N)(C)CSC.C1(=O)OC(=O)C2=CC=CC=C12.[CH3:19][C:20]([NH:25][C:26](=[O:36])[C:27]1[C:28](=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:29]([OH:31])=O)([CH3:24])[CH2:21][S:22][CH3:23].C(=O)([O-])O.[Na+].ClC(OC)=O.[CH3:47][C:48]1[CH:54]=[C:53]([C:55]([F:64])([C:60]([F:63])([F:62])[F:61])[C:56]([F:59])([F:58])[F:57])[CH:52]=[CH:51][C:49]=1[NH2:50].Cl>ClCCCl.C(N(CC)CC)C>[CH3:24][C:20]([NH:25][C:26]([C:27]1[C:28]([C:29]([NH:50][C:49]2[CH:51]=[CH:52][C:53]([C:55]([F:64])([C:56]([F:57])([F:58])[F:59])[C:60]([F:61])([F:62])[F:63])=[CH:54][C:48]=2[CH3:47])=[O:31])=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:36])([CH3:19])[CH2:21][S:22][CH3:23]

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformateHCID 6811Phthalic AnhydrideHCID 516892Sodium Bicarbonate2×HCID 99255434-(1,1,1,2,3,3,3-Heptafluoropropan-2-yl)-2-methylanilineHCID 11437082N-[1,1-dimethyl-2-(methylthio)ethyl]phthalamic acidHCID 120973802-Propanamine, 2-methyl-1-(methylthio)-

Product 1

HCID 22066226N-(1,1-Dimethyl-2-methylthioethyl)-N'-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]phthalamideYield 92%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

A mixture of 2-methyl-1-methylthio-2-propanamine (11.61 g) and triethylamine (1.97 g) was added dropwise to a mixture of phthalic anhydride (14.42 g) and 1,2-dichloroethane (58 mL) at 50° C. The resulting mixture was stirred at the same temperature for 30 minutes to prepare N-[1,1-dimethyl-2-(methylthio)ethyl]phthalamic acid. Aqueous sodium hydrogencarbonate solution (9.81 g/101 mL) was added dropwise to this mixture at 40° C. and then methyl chloroformate (11.04 g) was added dropwise thereto at the same temperature. After completion of the dropwise addition, the reaction mixture was stirred at 50° C. for 1 hour and the organic layer was separated to prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane. This solution was added dropwise to a mixture of 2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoro-methyl)ethyl]aniline (25.45 g), concentrated hydrochloric acid (0.49 g) and 1,2-dichloroethane (14.4 mL) at 60° C., and then stirred at 65° C. for 30 minutes. The reaction mixture was cooled and then neutralized with an aqueous sodium hydrogencarbonate solution, after which the organic layer was separated. The organic layer obtained was concentrated under reduced pressure, and the crystals precipitated were filtered, washed with water and then dried to obtain 47.06 g (yield 92%) of the title compound.

Workup

  1. additionAfter completion of the dropwise addition
  2. stirringthe reaction mixture was stirred at 50° C. for 1 hour
  3. customthe organic layer was separated
  4. customto prepare a solution of N-[1,1-dimethyl-2-(methylthio)ethyl]isophthalimide in 1,2-dichloroethane
  5. stirringstirred at 65° C. for 30 minutes
  6. temperatureThe reaction mixture was cooled
  7. customafter which the organic layer was separated
  8. customThe organic layer obtained
  9. concentrationwas concentrated under reduced pressure
  10. customthe crystals precipitated
  11. filtrationwere filtered
  12. washwashed with water
  13. customdried

Sources & evidence

ORD record
ord-6524f59788c141b3b9e38fde66526570
Source dataset
uspto-grants-2010_07
Patent number
US07763750B2

Reaction notes

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