tert-Butyl 3-butyn-1-ylcarbamate → tert-Butyl (2-(3-(3-chloro-4-cyanophenyl)isoxazol-5-yl)ethyl)carbamate

HRID 872831Notes

Reaction equation

[CH2:1]([NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])[CH2:2][C:3]#[CH:4].[Cl:13][C:14]1[CH:15]=[C:16]([CH:21]=[CH:22][C:23]=1[C:24]#[N:25])/[C:17](/Cl)=[N:18]/[OH:19]>C1(C)C=CC=CC=1.CN(C=O)C>[Cl:13][C:14]1[CH:15]=[C:16]([C:17]2[CH:4]=[C:3]([CH2:2][CH2:1][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:9])([CH3:11])[CH3:10])[O:19][N:18]=2)[CH:21]=[CH:22][C:23]=1[C:24]#[N:25]

Participants

Conditions

Temperature: 40 °C

Procedure

tert-Butyl but-3-yn-1-ylcarbamate (0.7 g, 4.14 mmol) was dissolved in toluene (20 ml) and trietyhylamine (0.87 ml) was added at RT. (Z)-3-chloro-4-cyano-N-hydroxybenzimidoyl chloride (0.98 g, 4.55 mmol) was added in DMF (2 ml) to reaction mixture. After one hour in RT the reaction mixture was heated to 40° C. for 2 h. The white precipitate was filtered and the filtrate was washed with 1 M HCl, water and brine. Dried over anhydrous Na2SO4, filtered and evaporated. The crude product was purified by Flash chromatography (Heptane-EtOAc 2:1). Product fractions were combined and evaporated to give pure title compound (0.78 g). 1H-NMR (400 MHz; d6-DMSO): δ 1.35 (s, 9H), 2.95 (t, 2H), 3.30 (m, 2H), 7.04 (m, 2H), 8.00 (d, 1H), 8.12 (d, 1H), 8.18 (s, 1H).

Workup

additiontrietyhylamine (0.87 ml) was added at RT
filtrationThe white precipitate was filtered
washthe filtrate was washed with 1 M HCl, water and brine
dry with materialDried over anhydrous Na2SO4
filtrationfiltered
customevaporated
customThe crude product was purified by Flash chromatography (Heptane-EtOAc 2:1)
customevaporated

Sources & evidence

ORD record: ord-9acbfb0202824ccb949626e524a75615
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08975254B2

Reaction notes

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