Ammonium Chloride → 4-(4-Hydroxytetrahydro-2H-pyran-4-yl)benzenecarbonitrile

HRID 1260182Notes

Reaction equation

HRID 1260182 reaction equation
C([Mg]Cl)(C)C.I[C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=1.[O:15]1[CH2:20][CH2:19][C:18](=[O:21])[CH2:17][CH2:16]1.[Cl-].[NH4+]>C(OCC)C.C1COCC1>[OH:21][C:18]1([C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=2)[CH2:19][CH2:20][O:15][CH2:16][CH2:17]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 764674-IodobenzonitrileHCID 121599Tetrahydro-4H-pyran-4-oneHCID 178418918HCID 178418918, compound

Product 1

HCID 595046634-(4-Hydroxytetrahydro-2H-pyran-4-yl)benzenecarbonitrile

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Under inert conditions, 109 ml (218 mmol) of a 2 M solution of isopropylmagnesium chloride in diethyl ether were added dropwise at −40° C. to a solution of 50.0 g (218 mmol) of 4-iodobenzonitrile in 1000 ml of anhydrous THF. After the mixture had been stirred at the same temperature for 1.5 h, a solution of 32.8 g (327 mmol) of tetrahydro-4H-pyran-4-one in 250 ml of anhydrous THF was added. After the addition had ended, the reaction mixture was stirred first at −40° C. for 10 min, then at 0° C. for 30 min and finally at RT for 60 min. Then approx. 20 ml of saturated aqueous ammonium chloride solution were added at −20° C. Subsequently, the solvent was substantially removed on a rotary evaporator. 1000 ml of water were added to the remaining residue, which was extracted three times with approx. 500 ml each time of dichloromethane. The combined organic extracts were washed successively with water and saturated sodium chloride solution. After drying over anhydrous magnesium sulphate, the mixture was filtered and the solvent was removed on a rotary evaporator. The resulting crude product was purified by stirring with 10:1 cyclohexane/ethyl acetate. 19.3 g (43% of theory) of the title compound were obtained.

Workup

  1. additionAfter the addition
  2. stirringthe reaction mixture was stirred first at −40° C. for 10 min
  3. waitat 0° C. for 30 min
  4. waitfinally at RT for 60 min
  5. customSubsequently, the solvent was substantially removed on a rotary evaporator
  6. addition1000 ml of water were added to the remaining residue, which
  7. extractionwas extracted three times with approx. 500 ml each time of dichloromethane
  8. washThe combined organic extracts were washed successively with water and saturated sodium chloride solution
  9. dry with materialAfter drying over anhydrous magnesium sulphate
  10. filtrationthe mixture was filtered
  11. customthe solvent was removed on a rotary evaporator
  12. customThe resulting crude product was purified
  13. stirringby stirring with 10:1 cyclohexane/ethyl acetate

Sources & evidence

ORD record
ord-3c606005a12d47b3bdc17053b152da25
Source dataset
uspto-grants-2013_06
Patent number
US08470811B2

Reaction notes

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