Hydrochloric Acid → 5-amino-3-cyano-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-benzamide

HRID 888460Notes

Reaction equation

HRID 888460 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([N+:30]([O-])=O)[CH:29]=1)[C:6]([NH:8][C:9]1[C:14]([CH3:15])=[CH:13][C:12]([C:16]([F:25])([C:21]([F:24])([F:23])[F:22])[C:17]([F:20])([F:19])[F:18])=[CH:11][C:10]=1[CH3:26])=[O:7])#[N:2].[Sn](Cl)(Cl)(Cl)Cl.Cl>C(O)(C)C>[NH2:30][C:28]1[CH:29]=[C:3]([C:1]#[N:2])[CH:4]=[C:5]([CH:27]=1)[C:6]([NH:8][C:9]1[C:10]([CH3:26])=[CH:11][C:12]([C:16]([F:25])([C:17]([F:18])([F:19])[F:20])[C:21]([F:22])([F:23])[F:24])=[CH:13][C:14]=1[CH3:15])=[O:7]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 24287Tin tetrachlorideHCID 592269403-cyano-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-5-nitro-benzamide

Product 1

HCID 592269545-amino-3-cyano-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-benzamideYield 94.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
0 °C

Procedure

3-Cyano-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-5-nitro-benzamide (12.0 g, 25.9 mmol) (Example I5) was dissolved in isopropanol (200 ml) and tin chloride (14.73 g, 77.7 mmol) was added. The mixture was cooled to 0° C. and aqueous hydrochloric acid (concentrated) (30 ml) was added slowly. The reaction mixture was stirred at 80° C. for 0.5 hours. ⅓ of the total volume of isopropanol was evaporated. Water (100 ml) was added to the concentrated mixture and aqueous sodium hydroxide (4N) was added to adjust the pH to 7-8. The aqueous phase was extracted three times with ethyl acetate (3×200 ml). The combined organic extracts were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 4:1 to 0:1) to give 5-amino-3-cyano-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-benzamide (10.6 g, 94.4% yield). 1H-NMR (400 MHz, CDCl3): 7.47 (s, 1H), 7.44 (s, 2H), 7.36 (s, 2H), 7.07 (s, 1H), 4.11 (bs, 2H), 2.32 (s, 6H) ppm.

Workup

  1. custom⅓ of the total volume of isopropanol was evaporated
  2. additionWater (100 ml) was added to the concentrated mixture and aqueous sodium hydroxide (4N)
  3. additionwas added
  4. extractionThe aqueous phase was extracted three times with ethyl acetate (3×200 ml)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 4:1 to 0:1)

Sources & evidence

ORD record
ord-fc74e3fd21b34c1dbe1c14c0fe15647c
Source dataset
uspto-grants-2012_08
Patent number
US08247594B2

Reaction notes

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