Cycloheptanol → 4-(Cycloheptyloxy)benzonitrile

HRID 2041515Notes

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

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

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

Sources & evidence

ORD record: ord-4ddab00f7e0a4270b51172d32f4795eb
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580780B2

Reaction notes

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