Isopropyl Acetate → HCID 16680143, compound

HRID 968877Notes

Reaction equation

HRID 968877 reaction equation
CC(C)([O-])C.[K+].[C:7]([CH2:9]P(=O)(OCC)OCC)#[N:8].[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([S:25]([C:28]2([C:35]3[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:36]=3[F:42])[CH2:33][CH2:32][C:31](=O)[CH2:30][CH2:29]2)(=[O:27])=[O:26])=[CH:21][CH:20]=1.C(OC(C)C)(=O)C>O1CCCC1.O>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([S:25]([C:28]2([C:35]3[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:36]=3[F:42])[CH2:29][CH2:30][C:31](=[CH:9][C:7]#[N:8])[CH2:32][CH2:33]2)(=[O:26])=[O:27])=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 7915Isopropyl AcetateHCID 75676Diethyl (cyanomethyl)phosphonateHCID 104301374-(4-chlorophenyl)sulfonyl-4-(2,5-difluorophenyl)cyclohexan-1-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 16680143HCID 16680143, compoundYield 87.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of potassium tert butoxide (1.0M in THF, 3.20 Kg, 3.55 mol) in tetrahydrofuran (2.1L) was added diethyl (cyanomethyl)phosphonate (642 g, 3.62 mol), maintaining the temperature below 5° C. The resulting solution was aged for 2 h and a solution of 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexanone (1.07 Kg, 2.78 mol) (Preparation 2) in tetrahydrofuran (3.9 L) was added. After the reaction was completed, isopropyl acetate (13.1 L) and water (26.3 L) were added. The organic layer was washed with brine and then concentrated to 1 L. Heptane (10.5 L) was added. The resulting solid was filtered, washed with heptane, dried in vacuo at 37° C. and then slurried in diethyl ether (5 L). Filtration and drying in vacuo afforded 989 g (87% yield) of [4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexylidene]acetonitrile. 1H NMR (CDCl3) 7.41-7.34 (4H, m), 7.25-7.06 (2H, m), 6.94-6.87 (1H, m), 5.12 (1H, s), 3.05-3.03 (1H, m), 2.92-2.86 (2H, m), 2.54-2.50 (1H, m), and 2.30-2.03 (4H, m).

Workup

  1. temperaturemaintaining the temperature below 5° C
  2. washThe organic layer was washed with brine
  3. concentrationconcentrated to 1 L
  4. additionHeptane (10.5 L) was added
  5. filtrationThe resulting solid was filtered
  6. washwashed with heptane
  7. customdried in vacuo at 37° C.
  8. filtrationFiltration
  9. customdrying in vacuo

Sources & evidence

ORD record
ord-ecef6557fef14a458a1e4f772821e5bb
Source dataset
uspto-grants-2007_12
Patent number
US07304094B2

Reaction notes

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