4-Fluorobenzonitrile → 4-(3,3-Dimethyl-1,5-dioxa-spiro[5.5]undec-9-yloxy)-benzonitrile

HRID 459915

Reaction equation

HRID 459915 reaction equation
[CH3:1][C:2]1([CH3:14])[CH2:7][O:6][C:5]2([CH2:12][CH2:11][CH:10]([OH:13])[CH2:9][CH2:8]2)[O:4][CH2:3]1.[H-].[Na+].F[C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=1>CN(C=O)C>[CH3:1][C:2]1([CH3:14])[CH2:3][O:4][C:5]2([CH2:8][CH2:9][CH:10]([O:13][C:18]3[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=3)[CH2:11][CH2:12]2)[O:6][CH2:7]1

Participants

5

Reactant 3

HCID 145174-FluorobenzonitrileHCID 24758Sodium hydrideHCID 124700963,3-Dimethyl-1,5-dioxaspiro[5.5]undecan-9-ol

Product 1

HCID 184452994-(3,3-Dimethyl-1,5-dioxa-spiro[5.5]undec-9-yloxy)-benzonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Add dropwise a solution of 3,3-dimethyl-1,5-dioxa-spiro[5.5]undecan-9-ol, (NE4-A05445-029, 1377 mg, 6.88 mmol) in DMF (2.0 mL) to a suspension of sodium hydride (412 mg, 10.32 mmol) in DMF (8.0 mL). Let the reaction mixture stir at room temperature for 1 h, then heat while stirring at 50° C. for 20 minutes (min). Add dropwise a solution of 4-fluoro-benzonitrile (1000 mg, 8.26 mmol) in DMF (4.2 mL). Continue the heating at 60° C. and stirring for 2 hours (h). Concentrate the reaction mixture to remove DMF. Wash the residue with water (15 mL) and extract with EtOAc/hexanes (20 mL). Dry the organic layer over sodium sulfate, filter and concentrate. Purify the residue by flash chromatography (eluent CH2Cl2/hexanes 2/1) to give xxx mg (xx % yield) of the title compound.

Workup

  1. temperatureheat
  2. stirringwhile stirring at 50° C. for 20 minutes (min)
  3. customheating at 60° C.
  4. stirringstirring for 2 hours (h)
  5. concentrationConcentrate the reaction mixture
  6. customto remove DMF
  7. washWash the residue with water (15 mL)
  8. extractionextract with EtOAc/hexanes (20 mL)
  9. dry with materialDry the organic layer over sodium sulfate
  10. filtrationfilter
  11. concentrationconcentrate
  12. customPurify the residue by flash chromatography (eluent CH2Cl2/hexanes 2/1)

Sources & evidence

ORD record
ord-72a2f0cc86f7491abb23184b8221f6c7
Source dataset
uspto-grants-2007_03
Patent number
US07196100B2

Linked notes

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