Triethylamine → 2-(5-Fluoro-2-((trimethylsilyl)ethynyl)phenyl)acetamide

HRID 1778990Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][C:10]([NH2:12])=[O:11].F[B-](F)(F)F.[CH3:18][Si:19]([C:22]#[CH:23])([CH3:21])[CH3:20].CCN(CC)CC>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:23]#[C:22][Si:19]([CH3:21])([CH3:20])[CH3:18])=[C:3]([CH2:9][C:10]([NH2:12])=[O:11])[CH:4]=1

Participants

Conditions

Temperature: 65 °C

Procedure

Under inert conditions a suspension of 2-(2-bromo-5-fluorophenyl)acetamide (A33) (0.242 g, 1.04 mmol), PdCl2(PPh3)2 (0.037 g, 0.052 mmol), t-Bu3PH.BF4 (0.015 g, 0.052 mmol), CuI (0.010 g, 0.052 mmol) and (trimethylsilyl)acetylene (0.177 mL, 1.25 mmol) in anhydrous DMF (9 mL) was degassed with nitrogen for 10 minutes. Et3N (3 mL) was added and the resulting mixture was stirred at 65° C. under nitrogen for 16 hours. The volatiles were removed under reduced pressure, then the residue adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.) to give the title compound A34 as a tan coloured solid (0.242 g, 93%); 1H NMR (400 MHz, d6-DMSO) δ 7.46 (dd, J=8.6, 5.9 Hz, 1H), 7.38 (s, 1H), 7.15 (dd, J=10.0, 2.7 Hz, 1H), 7.08 (td, J=8.6, 2.7 Hz, 1H), 6.99 (s, 1H), 3.60 (s, 2H), 0.23 (s, 9H).

Workup

customThe volatiles were removed under reduced pressure
custompurified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record: ord-d288641dc7ba409d92b63bc374f9874e
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266864B2

Reaction notes

Loading…