1,1'-Carbonyldiimidazole → 4-(3-Chloro-4-fluorophenyl)-3-(4-[(triisopropylsilyl)oxy]methyl-1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazol-5(4H)-one

HRID 2097610Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([C:13]2[C:17]([CH2:18][O:19][Si:20]([CH:27]([CH3:29])[CH3:28])([CH:24]([CH3:26])[CH3:25])[CH:21]([CH3:23])[CH3:22])=[N:16][O:15][N:14]=2)=[N:11][OH:12])[CH:5]=[CH:6][C:7]=1[F:8].C1N=CN([C:35](N2C=NC=C2)=[O:36])C=1>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:35](=[O:36])[O:12][N:11]=[C:10]2[C:13]2[C:17]([CH2:18][O:19][Si:20]([CH:24]([CH3:26])[CH3:25])([CH:27]([CH3:29])[CH3:28])[CH:21]([CH3:22])[CH3:23])=[N:16][O:15][N:14]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

Conditions

Temperature: 70 °C

Procedure

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(triisopropylsilyl)oxy]methyl-1,2,5-oxadiazole-3-carboximidamide (2.2 g, 5.0 mmol) was dissolved in anhydrous tetrahydrofuran (THF) (31 mL) followed by addition of N,N-carbonyldiimidazole (980 mg, 6 mmol). The reaction was heated to 70° C. and monitored by LCMS. Another 0.5 eq of N,N-carbonyldiimidazole was added and the reaction was stirred overnight at 70° C. The reaction was cooled and concentrated in vacuo. The crude oil was dissolved in chloroform and loaded onto a 120 g ISCO cartridge, eluted with 25% EtOAc/Hexane. The combined fractions were stripped to dryness to give the desired product as a white solid (1.74 g, 73%). 1H NMR (400 MHz, DMSO-d6) δ: 7.95 (m, 1H), 7.65 (m, 1H), 7.64 (m, 1H), 5.12 (s, 2H), 1.14 (m, 3H), 1.04 (d, J=7.0 Hz, 18H); MF═C20H26ClFN4O4Si; LCMS calculated for C20H27ClFN4O4Si(M+H)+: m/z=469.147.

Workup

temperatureThe reaction was cooled
concentrationconcentrated in vacuo
dissolutionThe crude oil was dissolved in chloroform
washeluted with 25% EtOAc/Hexane

Sources & evidence

ORD record: ord-f5dd70aa87fc40e5b9e51a0d8ecacc18
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08450351B2

Reaction notes

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