Hydrochloric Acid → 5-[5-(4-Cyanophenoxy)pentyl]-3-methylisoxazole

HRID 2165374Notes

Reaction equation

[CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[O:4][N:3]=1.C([Li])CCC.Br[CH2:14][CH2:15][CH2:16][CH2:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=1.[Cl-].[Na+].Cl>O1CCCC1.C(OCC)(=O)C>[C:23]([C:22]1[CH:25]=[CH:26][C:19]([O:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:7][C:5]2[O:4][N:3]=[C:2]([CH3:1])[CH:6]=2)=[CH:20][CH:21]=1)#[N:24]

Participants

Conditions

Temperature: -70 °C

Procedure

To a solution of 5.86 g of 3,5-dimethylisoxazole in 120 ml of dry tetrahydrofuran at -70° C. under nitrogen was added during 14 minutes 36 ml of n-butyllithium (1.7M in hexane). The mixture was stirred at -70° C. for 30 minutes, and then 15.2 g of 4-(4-bromobutyloxy)benzonitrile in 40 ml of tetrahydrofuran was added over a 15 minute period. The reaction mixture was stirred for 1.5 hours at -70° C. and then allowed to warm to room temperature and stirred for 2.5 hours longer. Evaporation of the solvent gave a residue which was treated with 300 ml of ethyl acetate, 150 ml of concentrated sodium chloride solution and 12 ml of hyrochloric acid. The material which was soluble in ethyl acetate was isolated, combined with material from another run of the same scale and subjected to high pressure liquid chromatography with ether-hexane (1:1) to give 20 g of 5-[5-(4-cyanophenoxy)pentyl]-3-methylisoxazole as a colorless solid, m.p. 57° C.

Workup

stirringThe reaction mixture was stirred for 1.5 hours at -70° C.
temperatureto warm to room temperature
stirringstirred for 2.5 hours longer
customEvaporation of the solvent
customgave a residue which
customwas isolated

Sources & evidence

ORD record: ord-f91989ef2b444baeba86bac48ed4c51d
Source dataset: uspto-grants-1990_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04939267

Reaction notes

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