Isopropanol → HCID 86709878, compound

HRID 541053Notes

Reaction equation

HRID 541053 reaction equation
ClC1C(Cl)=C(C2C=CC(Cl)=CC=2)N=C(C(Cl)=O)C=1.[F-].[K+].[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[N:33]=[C:32]([C:34](F)=[O:35])[CH:31]=[C:30]([F:37])[C:29]=2[F:38])=[CH:24][CH:23]=1.C(N(CC)CC)C.[CH:46]([OH:49])([CH3:48])[CH3:47]>S1(CCCC1)(=O)=O.O>[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[N:33]=[C:32]([C:34]([O:49][CH:46]([CH3:48])[CH3:47])=[O:35])[CH:31]=[C:30]([F:37])[C:29]=2[F:38])=[CH:24][CH:23]=1

Participants

8

Reactant 5

HCID 3776IsopropanolHCID 8471TriethylamineHCID 522689Potassium FluorideHCID 86709874HCID 86709874, compoundHCID 86709879HCID 86709879, compound

Product 1

HCID 86709878HCID 86709878, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31347SulfolaneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 4,5-dichloro-6-(4-chlorophenyl)picolinoyl chloride (2.0 g, 6.23 mmol) in sulfolane (40 mL, dried over 4 Å molecular sieves, 100 ppm H2O) was added potassium fluoride (2.2 g, 37.4 mmol). The reaction mixture was heated at 130° C. for 24 h. Reaction mixture was analyzed by GC-MS and 19F NMR. Data for 6-(4-chlorophenyl)-4,5-difluoropicolinoyl fluoride, GC-MS: m/z=271, 223; 19F NMR (376 MHz, Toluene-d8) δ 17.05 (s), −123.81 (d, J=19.1 Hz), −140.17 (d, J=19.1 Hz). Reaction was allowed to cool to room temperature and triethylamine (1.1 mL, 7.8 mmol) and isopropanol (0.7 mL, 9.4 mmol) were added. After stirring for 1.5 h, the reaction mixture was diluted with water (100 mL) and transferred to a reparatory 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 0.93 g (48% yield) of isopropyl 6-(4-chlorophenyl)-4,5-difluoropicolinate as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.04-7.98 (m, 2H), 7.90 (dd, J=9.4, 5.3 Hz, 1H), 7.51-7.45 (m, 2H), 5.31 (hept, J=6.3 Hz, 1H), 1.43 (d, J=6.3 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 162.72 (d, J=3.5 Hz), 158.12 (d, J=12.6 Hz), 155.49 (d, J=12.4 Hz), 149.41 (d, J=11.0 Hz), 147.16 (dd, J=7.9, 1.0 Hz), 146.73 (d, J=10.9 Hz), 136.51 (d, J=0.9 Hz), 130.34 (d, J=6.6 Hz), 128.93 (s), 113.80 (d, J=16.1 Hz), 70.25 (s), 21.85 (s); 19F NMR (376 MHz, CDCl3) δ −124.73 (dd, J=17.7, 9.5 Hz), −144.38 (dd, J=17.7, 5.4 Hz); MS Calcd. for C16H15F2NO3: 307.10. Found: 307 (M+), 221, 206; mp=73-74° C.

Workup

  1. customReaction mixture
  2. customReaction
  3. temperatureto cool to room temperature
  4. customtransferred to a reparatory 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-1c8504a2ee7c4a9d9a17ddce9eab945c
Source dataset
uspto-grants-2014_10
Patent number
US08871943B2

Reaction notes

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