Water → 5-{4-[2-(Trifluoromethyl)phenoxy]piperidin-1-yl}-1,3,4-thiadiazole-2-carbonitrile

HRID 561192Notes

Reaction equation

[F:1][C:2]([F:23])([F:22])[C:3]1[CH:21]=[CH:20][CH:19]=[CH:18][C:4]=1[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[S:16][C:15](N)=[N:14][N:13]=2)[CH2:8][CH2:7]1.[C:24]([Cu])#[N:25].O.C(Cl)Cl>CC#N>[F:23][C:2]([F:22])([F:1])[C:3]1[CH:21]=[CH:20][CH:19]=[CH:18][C:4]=1[O:5][CH:6]1[CH2:7][CH2:8][N:9]([C:12]2[S:16][C:15]([C:24]#[N:25])=[N:14][N:13]=2)[CH2:10][CH2:11]1

Participants

Conditions

Temperature: 55 °C

Procedure

To a suspension of 5-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3,4-thiadiazol-2-amine (10.0 g, 29.0 mmol) in CH3CN (150 mL) was added CuCN (5.3 g, 59.2 mmol) and t-BuONO (90%) (8 mL, 60.0 mmol) at room temperature. The reaction mixture was heated at 50-60° C. for 2 h until TLC indicated disappearance of the starting material. The reaction mixture was poured into water and CH2Cl2 was added. The solid was removed by filtration and the filtrate was extracted with CH2Cl2, dried (Na2SO4) and filtered. Solvents were removed in vacuo to afford the crude product, which was purified by column chromatography on silica gel (eluting with 5:1 petroleum ether/EtOAc) to afford the title compound. 1H NMR (400 MHz, CDCl3): δ7.61 (d, 1H), 7.50 (t, 1H), 6.93-7.06 (m, 2H), 4.86 (br s, 1H), 3.77-3.83 (m, 4H), 2.01-2.20 (m, 4H). MS: m/z 355 (MH+).

Workup

customat room temperature
additionwas added
customThe solid was removed by filtration
extractionthe filtrate was extracted with CH2Cl2
dry with materialdried (Na2SO4)
filtrationfiltered
customSolvents were removed in vacuo
customto afford the crude product, which
customwas purified by column chromatography on silica gel (eluting with 5:1 petroleum ether/EtOAc)

Sources & evidence

ORD record: ord-4b5e9e9fd43747c19b0e629a6ab7db9c
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063224B2

Reaction notes

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