Isopropanol → HCID 89942768, compound

HRID 2206978Notes

Reaction equation

HRID 2206978 reaction equation
ClC1C(Cl)=C(C2C=CC=CC=2)N=C(C(Cl)=O)C=1.[F-].[K+].[F:20][C:21]1[C:26]([F:27])=[C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:24]=[C:23]([C:34](F)=[O:35])[CH:22]=1.C(N(CC)CC)C.[CH:44]([OH:47])([CH3:46])[CH3:45]>S1(CCCC1)(=O)=O.O>[F:20][C:21]1[C:26]([F:27])=[C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:24]=[C:23]([C:34]([O:47][CH:44]([CH3:46])[CH3:45])=[O:35])[CH:22]=1

Participants

8

Reactant 5

HCID 3776IsopropanolHCID 8471TriethylamineHCID 522689Potassium FluorideHCID 86709875HCID 86709875, compoundHCID 89943386HCID 89943386, compound

Product 1

HCID 89942768HCID 89942768, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31347SulfolaneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 4,5-dichloro-6-phenylpicolinoyl chloride (1.76 g, 6.14 mmol) in sulfolane (40 mL, dried over 4 Å molecular sieves, ˜100 ppm H2O) was added potassium fluoride (2.14 g, 36.9 mmol). The reaction mixture was heated at 130° C. for 24 h. Reaction mixture was analyzed by GC-MS and 19F NMR. (Data for 4,5-difluoro-6-phenylpicolinoyl fluoride, GC-MS: m/z=237, 189; 19F NMR (376 MHz, Toluene-d8) δ 17.03 (s), −124.14 (d, J=19.1 Hz), −140.76 (d, J=19.1 Hz). Reaction was allowed to cool to room temperature and triethylamine (1.1 mL, 7.7 mmol) and isopropanol (0.7 mL, 9.2 mmol) were added. After stirring for 1.5 h, the reaction mixture was diluted with water (100 mL) and transferred to a separatory funnel. The reaction mixture was extracted with methyl tert-butyl ether (MTBE, 2×50 mL). The combined organic extracts were washed with water (3×50 mL) and saturated NaCl (50 mL) and concentrated under reduced pressure to provide a brown oil. The crude product oil was purified by silica gel flash chromatography (hexane/ethyl acetate gradient, 100% hexane→20% hexane/ethyl acetate) to provide 1.2 g (70% yield) of isopropyl 4,5-difluoro-6-phenyl-picolinate as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.07-7.99 (m, 2H), 7.89 (dd, J=9.4, 5.3 Hz, 1H), 7.56-7.42 (m, 3H), 5.31 (hept, J=6.3 Hz, 1H), 1.43 (d, J=6.3 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 162.89 (d, J=3.4 Hz), 156.74 (dd, J=264.2, 12.5 Hz), 148.07 (dd, J=268.9, 10.8 Hz), 146.99 (dd, J=309.2, 10.8 Hz), 145.45 (s), 134.12-133.60 (m), 130.20 (s), 129.05 (d, J=5.9 Hz), 128.64 (s), 113.56 (d, J=16.0 Hz), 70.14 (s), 21.86 (s). 19F NMR (376 MHz, CDCl3) δ −125.22 (dd, J=17.7, 9.5 Hz), −144.74 (dd, J=17.7, 5.4 Hz). LRMS. Calcd. C15H13F2—NO2: 277.09. Found: m/z=277 (M+), 218, 191.

Workup

  1. customReaction mixture
  2. customReaction
  3. temperatureto cool to room temperature
  4. customtransferred to a separatory funnel
  5. extractionThe reaction mixture was extracted with methyl tert-butyl ether (MTBE, 2×50 mL)
  6. washThe combined organic extracts were washed with water (3×50 mL) and saturated NaCl (50 mL)
  7. concentrationconcentrated under reduced pressure
  8. customto provide a brown oil
  9. customThe crude product oil was purified by silica gel flash chromatography (hexane/ethyl acetate gradient, 100% hexane→20% hexane/ethyl acetate)

Sources & evidence

ORD record
ord-63192dda31ae46679114f735a8494448
Source dataset
uspto-grants-2016_06
Patent number
US09376388B2

Reaction notes

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