Sodium hydride → HCID 11695104, compound

HRID 2243196Notes

Reaction equation

HRID 2243196 reaction equation
[CH3:1][C:2]1([CH3:9])[C@@H:7]([OH:8])[C:5](=[O:6])[O:4][CH2:3]1.[H-].[Na+].[H][H].F[C:15]1[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[C:17]([C:23]([F:26])([F:25])[F:24])[CH:16]=1.[Cl-].[NH4+]>O1CCCC1>[CH3:1][C:2]1([CH3:9])[CH2:3][O:4][C:5](=[O:6])[CH:7]1[O:8][C:15]1[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[C:17]([C:23]([F:24])([F:26])[F:25])[CH:16]=1

Participants

7

Reactant 5

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 439368D-PantolactoneHCID 6050854-Fluoro-2-(trifluoromethyl)benzonitrileHCID 178418361HCID 178418361, compound

Product 1

HCID 11695104HCID 11695104, compoundYield 106.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution comprised of (R)-(−)-pantolactone (44.7 g; 336 mmol) in tetrahydrofuran (625 mL) at 0° C. under a nitrogen atmosphere was added a 60% sodium hydride mineral oil dispersion (14.1 g; 352 mmol) directly in portions. Upon the completion of hydrogen gas liberation, 4-fluoro-2-trifluoromethylbenzonitrile solid (59.0 g; 312 mmol) was added directly. The reaction mixture was allowed to warm slowly to ambient temperature overnight. The reaction mixture was neutralized with saturated aqueous ammonium chloride (500 mL.) The mixture was extracted with ethyl acetate (800 mL) and the layers were separated. The organic layer was dried over anhydrous magnesium sulfate and was concentrated in vacuo to afford 99.83 g of a beige solid. The solid was recrystallized from absolute ethanol (300 mL) to afford 81.56 g of an off-white crystalline solid; 1H-NMR (400 MHz; CDCl3) δ 7.78 (dd, 1H, J=8.6, 0.4 Hz), 7.43 (d, 1H, J=2.5 Hz), 7.31 (dd, 1H, J=8.6, 2.7 Hz), 4.67 (s, 3H), 4.17 (d, 1H, J=9.0 Hz), 4.10 (d, 1H, J=9.0 Hz), 1.29 (s, 6H); 19F-NMR (376 MHz; CDCl3) δ-62.70 (s, 3F).

Workup

  1. extractionwas extracted with ethyl acetate (800 mL)
  2. customthe layers were separated
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. concentrationwas concentrated in vacuo

Sources & evidence

ORD record
ord-9fe0dd9c22c3431fafa8a553aaaa4880
Source dataset
uspto-grants-2010_03
Patent number
US07674819B2

Reaction notes

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