Acetic Acid → 2-(5-Allyl-6-ethyl-pyridin-3-ylmethyl)-4,5,7-trifluoro-benzothiazole

HRID 900974Notes

Reaction equation

HRID 900974 reaction equation
[CH2:1]([C:4]1[CH:5]=[C:6]([CH2:12][C:13]#[N:14])[CH:7]=[N:8][C:9]=1[CH2:10][CH3:11])[CH:2]=[CH2:3].Cl.N[C:17]1[C:22]([F:23])=[C:21]([F:24])[CH:20]=[C:19]([F:25])[C:18]=1[SH:26].C(O)(=O)C.C(=O)(O)[O-].[Na+]>FC(F)(F)CO.C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C>[CH2:1]([C:4]1[CH:5]=[C:6]([CH2:12][C:13]2[S:26][C:18]3[C:19]([F:25])=[CH:20][C:21]([F:24])=[C:22]([F:23])[C:17]=3[N:14]=2)[CH:7]=[N:8][C:9]=1[CH2:10][CH3:11])[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 11390282Benzenethiol, 2-amino-3,4,6-trifluoro-, hydrochlorideHCID 596988125-Allyl-6-ethyl-pyridin-3-yl-acetonitrile

Product 1

HCID 596988202-(5-Allyl-6-ethyl-pyridin-3-ylmethyl)-4,5,7-trifluoro-benzothiazoleYield 87%

Reagents, catalysts & solvents 2

HCID 314042,6-Di-tert-butyl-4-methylphenolCatalystHCID 64092,2,2-TrifluoroethanolSolvent

Procedure

In a teflon screwcap glass pressure vessel a solution of 5-allyl-6-ethyl-pyridin-3-yl-acetonitrile (0.70 g, 3.76 mmol), 2-amino-3,4,6-trifluoro-benzenethiol hydrochloride (1.2 g, 5.64 mmol), 2,6-di-tert-butyl-4-methylphenol (BHT) (20 mg) and acetic acid (0.25 mL, 4.51 mmol) in 2,2,2-trifluoroethanol (5 mL, 0.8 M, degassed with nitrogen) is warmed to 90° C. and stirred overnight. The mixture is cooled to room temperature, added to saturated aq sodium bicarbonate (15 mL), extracted with ethyl acetate (2×15 mL) and dried over sodium sulfate. Purification by medium-pressure liquid chromatography (MPLC) on silica (20-40% ethyl acetate in heptane) provided 2-(5-allyl-6-ethyl-pyridin-3-ylmethyl)-4,5,7-trifluoro-benzothiazole as a yellow oil (1.14 g, 87%): Rf 0.38 (30% ethyl acetate in n-heptane), 1H NMR (CDCl3, 300 MHz) δ 8.45 (d, J=2.1 Hz, 1 H), 7.44 (d, J=2.1 Hz, 1 H), 7.01 (ddd, J1=10.5 Hz, J2=8.7 Hz, J3=5.6 Hz, 1 H), 5.91 (ddt, J1=17.0 Hz, J2=10.3 Hz, J3=6.3 Hz, 1 H), 5.13 (dd, J1=10.3 Hz, J2=1.5 Hz, 1 H), 5.01 (dd, J1=17.0 Hz, J2=1.5 Hz, 1 H), 3.40 (d, J=6.3 Hz, 2 H), 2.83 (q, J=7.5 Hz, 2 H), 1.29 (t, J=7.5 Hz, 3 H); ESI-LCMS m/z calcd for C18H15F3N2S: 348.1; found 349.0 (M+1)+.

Workup

  1. extractionextracted with ethyl acetate (2×15 mL)
  2. dry with materialdried over sodium sulfate
  3. customPurification by medium-pressure liquid chromatography (MPLC) on silica (20-40% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-9ad5ad81cbcb4215ad86700d44a45959
Source dataset
uspto-grants-2008_04
Patent number
US07361671B2

Reaction notes

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