Isoamylamine → HCID 86754513, compound

HRID 618788Notes

Reaction equation

HRID 618788 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:4]=[C:5]([N:13]=[C:14]=S)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[C:18]([CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])#[N:19].S([O-])([O-])(=O)=O.[Mg+2].[CH2:34]([NH2:39])[CH2:35][CH:36](C)[CH3:37]>[Hg]=O.C(Cl)Cl>[C:24]([O:23][C:21](=[O:22])[C:20]([C:18]#[N:19])=[C:14]([NH:13][C:5]1[CH:4]=[C:3]([C:2]([F:17])([F:16])[F:1])[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=1)[NH:19][CH2:18][CH2:20][CH2:21][N:39]1[CH2:34][CH2:35][CH2:36][CH2:37][CH2:25][C:24]1=[O:23])([CH3:27])([CH3:26])[CH3:25]

Participants

7

Reactant 4

HCID 7894IsoamylamineHCID 24083Sulfuric acid magnesium salt (1:1)HCID 70693tert-Butyl cyanoacetateHCID 27333953,5-Bis(trifluoromethyl)phenyl isothiocyanate

Product 1

HCID 86754513HCID 86754513, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 30856Mercuric oxideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3,5-bis(trifluoromethyl)phenylisothiocyanate (2.83 g, 10.4 mmol), DCM (20 mL) and tert-butyl cyanoacetate (1.65 mL, 11.6 mmol) DBU (4.0 mL, 26.8 mmol) was added, whereby an exothermic reaction occurred. The resulting mixture was stirred at room temperature for 2 h, and then magnesium sulfate (2.0 g), isoamylamine (2.35 mL) and mercury(II) oxide (6.80 g, 31.4 mmol) were added. After stirring for 25 h, the mixture was mixed with celite, filtered, and the filtrate was mixed with 0.5 M hydrochloric acid. After an additional filtration the filtrate was extracted (3×100 mL DCM), the combined extracts were washed with brine (2×300 mL, emulgates strongly), dried (magnesium sulfate) and concentrated. Column chromatography (80 g silica gel, gradient elution with heptane/ethyl acetate 10:0 to 2:3) gave 2.23 g (39%) of the title compound as a colourless solid, along with 0.72 g (15%) of 3-[3,5-bis(trifluoromethyl)phenylamino]-2-cyano-3-(3-methylbutylamino)acrylic acid tert-butyl ester. A sample of the title compound was further purified by recrystallization. Colourless solid, mp. 167-168° C. (ethyl acetate). LCMS: elution at 15.4 min, MH+ : 549; 1H NMR (400 MHz, DMSO-d6): δ=1.40 (s, 9H), 1.43 (m, 4H), 1.57 (m, 2H), 1.71 (q, J=7 Hz, 2H), 2.35 (m, 2H), 3.20 (q, J=7 Hz, 2H), 3.31 (m, 2H), 7.66 (s, 2H), 7.68 (s, 1H), 8.95 (s, br, 1H), 9.52 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ=22.93, 27.93, 28.11, 28.32, 29.23, 36.44, 41.55, 44.47, 48.38, 61.93, 79.66, 115.36, 118.75, 119.89, 123.18 (q, J=275 Hz), 131.02 (q, J=33 Hz), 142.33, 160.59, 167.95, 174.74. Anal. Calcd. for C25H30F6N4O3 (548.53): C, 54.74; H, 5.51; N, 10.21. Found: C, 54.62; H, 5.66; N, 9.97.

Workup

  1. additionwas added
  2. customwhereby an exothermic reaction
  3. stirringAfter stirring for 25 h
  4. additionthe mixture was mixed with celite
  5. filtrationfiltered
  6. additionthe filtrate was mixed with 0.5 M hydrochloric acid
  7. filtrationAfter an additional filtration the filtrate
  8. extractionwas extracted (3×100 mL DCM)
  9. washthe combined extracts were washed with brine (2×300 mL
  10. dry with materialdried (magnesium sulfate)
  11. concentrationconcentrated
  12. washColumn chromatography (80 g silica gel, gradient elution with heptane/ethyl acetate 10:0 to 2:3)

Sources & evidence

ORD record
ord-2ef33252ad72492c96dc326a7efc1cc3
Source dataset
uspto-grants-1999_09
Patent number
US05955548

Reaction notes

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