Cycloheptanol → 4-(Cycloheptyloxy)benzonitrile

HRID 911651Notes

Reaction equation

HRID 911651 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[CH:10]1(O)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.C(P(CCCC)CCCC)CCC.N1CCCCC1.N1CCCCC1.N(C(O)=O)=NC(O)=O>CCOC(C)=O.O.C1COCC1>[CH:10]1([O:1][C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

8

Reactant 4

HCID 10399CycloheptanolHCID 130194-CyanophenolHCID 13831TributylphosphineHCID 66707187Azodicarboxylate dipiperidine

Product 1

HCID 576566254-(Cycloheptyloxy)benzonitrileYield 58%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Under a nitrogen atmosphere, add 4-hydroxybenzonitrile (4 g, 33.5 mmol), cycloheptanol (2.55 g, 22.3 mmol), tri-n-butylphosphine (8.25 mL, 33.5 mmol), and azodicarboxylate dipiperidine (8.45 g, 33.5 mmol) to anhydrous THF (60 mL) at 0° C. Stir the mixture at 0° C. for 1 h and then at room temperature for 12 h. Dilute with EtOAc (50 mL) and water (50 mL). Separate the layers and extract the aqueous phase with EtOAc (4×30 mL). Wash the combined organic extracts with water (30 mL) and brine (20 mL). Dry over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel (120 g RediSep column) eluting with hexane/EtOAc (1:0 to 1:1 gradient over 1.25 h; 80 mL/min) to provide the desired intermediate as a colorless oil (2.77 g, 58%). MS (APCI) m/z: 216 (M+H)+.

Workup

  1. waitat room temperature for 12 h
  2. customSeparate the layers
  3. extractionextract the aqueous phase with EtOAc (4×30 mL)
  4. washWash the combined organic extracts with water (30 mL) and brine (20 mL)
  5. dry with materialDry over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify the crude mixture by chromatography on silica gel (120 g RediSep column)
  9. washeluting with hexane/EtOAc (1:0 to 1:1 gradient over 1.25 h; 80 mL/min)

Sources & evidence

ORD record
ord-f222f151b4c24039887e27f997028623
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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