Isopropyl iodide → HCID 18687764, compound

HRID 1872869Notes

Reaction equation

HRID 1872869 reaction equation
C(N(CC)C(=S)[O-])C.NN.O.[F:12][C:13]1[C:26]2[S:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[O:18][C:17]=2[CH:16]=[C:15]([OH:27])[C:14]=1[F:28].I[CH:30]([CH3:32])[CH3:31].C([O-])([O-])=O.[Cs+].[Cs+]>CCO.CCOC(C)=O.CCOCC.O.CN(C=O)C>[F:12][C:13]1[C:26]2[S:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[O:18][C:17]=2[CH:16]=[C:15]([O:27][CH:30]([CH3:32])[CH3:31])[C:14]=1[F:28]

Participants

11

Reactant 5

HCID 6362Isopropyl iodideHCID 10796Cesium carbonateHCID 24654Hydrazine hydrate (1:1)HCID 18687738HCID 18687738, compoundHCID 178464353HCID 178464353, compound

Product 1

HCID 18687764HCID 18687764, compoundYield 91%

Reagents, catalysts & solvents 5

HCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of O-[1,2-difluoro)phenoxathiin-3yl] N,N-diethylthiocarbamate (200 mg, 0.54 mmol) (Example 16) and H2NNH2.H2O (2.64 mL, 54.4 mmol) in 20 mL absolute EtOH was refluxed for 2 h. After cooling, to room temperature the reaction was diluted with EtOAc (75 mL), washed with 10% aqueous HCl (100 mL) and brine (100 mL), dried (Na2SO4), and concentrated in vacuo to 130 mg of crude 1,2-difluoro-3-phenoxathiinol as a yellow-brown solid: TLC (EtOAc/hexane, 40:60) Rf =0.46; 1H-NMR (CDCI3) δ 6.53 (dd. J=6 Hz, J=2 Hz, 1 H, C4 -H), δ 6.97-7.15 (m, 4 H). A mixture of crude 1,2-difluoro-3-phenoxathiinol (110 mg, 0.44 mmol), 2-iodopropane (0.09 ml, 0.87 mmol), Cs2CO3 (0.28 g, 0.87 mmol) and 7 ml anhydrous DMF was stirred under nitrogen at 0° C. for 5 h. The reaction was diluted with Et2O (50 ml) and water (50 ml), the Et2O fraction washed with brine (50 ml), dried (Na2SO4), and concentrated in vacuo to 118 mg of an orange oil. Filtration of the crude product through 10 g of silica gel with 200 ml of EtOAc/hexane (5:95) gave 116 mg (91%) of 1,2-difluoro-3-isopropoxyphenoxathiin as a pale orange oil: TLC (EtOAc/hexane, 20:80) Rf =0.58; 1H-NMR (CDCI3) δ 1.36 (d, J=6 Hz, 6 H), δ 4.50 (m, J=6 Hz H), δ 6.50 (dd, J=Hz, J=2 Hz, 1 H, C4 -H), δ 6.96-7.15 (m, 4 H); 19F-NMR (CDCI3) C1 -F (d, J=21.4 Hz), C2 -F (dd, J=21.4 Hz, J=6 Hz). A solution of 1,2-difluoro-3-isopropoxyphenoxathiin (112 mg, 0.38 mmol) and 30% aqueous H2O2 (0.4 ml, 3.8 mmol) in 3 ml glacial AcOH was heated at 80° C. for 2.5 h. After cooling to room temperature the solution was concentrated in vacuo to a white solid. Refrigeration of the crude product in 4 ml of 1:1 EtOAc/hexane overnight afforded 79 mg (44% from O-[1,2-(difluoro)phenoxathiin-3-yl] N,N-diethylthio-carbamate) of the title compound as yellow crystals: mp 174-175° C. (EtOAc/hexane); 1H-NMR (DMSO-d6) δ 1.33 (d, J=6 Hz, 6 H), δ 4.94 (m, J=6 Hz, 1 H), δ 7.31 (dd, J=6 Hz, J=2 Hz, 1 H, C4 -H), δ 7.30-7.57 (m, 2 H), δ 8.04 (dt, J=7 Hz, J=1 Hz, 1H, C8 -H), δ 8.06 (dd, J=8 Hz, J=1 Hz, 1 H, C9 -H); 19F-NMR (DMSO-d6) C1 -F (dd, J=21.2 Hz, J=6 Hz); MS m/e (relative intensity) 327 (MH+, 100).

Workup

  1. temperaturewas refluxed for 2 h
  2. washwashed with 10% aqueous HCl (100 mL) and brine (100 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo to 130 mg of crude 1,2-difluoro-3-phenoxathiinol as a yellow-brown solid
  5. washthe Et2O fraction washed with brine (50 ml)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo to 118 mg of an orange oil
  8. filtrationFiltration of the crude product through 10 g of silica gel with 200 ml of EtOAc/hexane (5:95)

Sources & evidence

ORD record
ord-433ff48ededc4a20af0d6fe1391d4223
Source dataset
uspto-grants-2000_08
Patent number
US06110961

Reaction notes

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