Triethylamine → N-(2-Fluoro-5-trimethylsilanylethynylbenzyl)-acetamide

HRID 606812Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([F:13])=[C:6]([CH:12]=1)[CH2:7][NH:8][C:9](=[O:11])[CH3:10].C(N(CC)CC)C.[CH3:21][Si:22]([C:25]#[CH:26])([CH3:24])[CH3:23]>O1CCCC1.[Br-].[Zn+2].[Br-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:13][C:5]1[CH:4]=[CH:3][C:2]([C:26]#[C:25][Si:22]([CH3:24])([CH3:23])[CH3:21])=[CH:12][C:6]=1[CH2:7][NH:8][C:9](=[O:11])[CH3:10]

Participants

Conditions

Temperature: 60 °C

Procedure

Combine N-(5-bromo-2-fluorobenzyl)acetamide, (prepared as described in PREPARATION 30), (370 mg, 1.50 mmol, zinc(II) bromide (588 mg, 2.25 mmol), and triethylamine (1.00 mL, 7.20 mmol) in tetrahydrofuran (3.7 mL). After stirring for 5 min, add trimethylsilylacetylene (0.53 mL, 3.76 mmol) and tetrakis(triphenylphosphine)palladium (0) (87 mg, 0.075 mmol). Heat the mixture in a sealed tube at 60° C. overnight. Cool the reaction to room temperature and filter through diatomaceous earth. Concentrate the filtrate and purify the residue by silica gel chromatography, eluting with a gradient from 75:25 to 65:35 with a solution of (1:1 hexanes and dichloromethane):ethyl acetate to give the title compound as a yellow oil which crystallizes upon standing (309 mg, 78%).

Workup

temperatureCool
customthe reaction to room temperature
filtrationfilter through diatomaceous earth
concentrationConcentrate the filtrate
custompurify the residue by silica gel chromatography
washeluting with a gradient from 75:25 to 65:35 with a solution of (1:1 hexanes and dichloromethane)

Sources & evidence

ORD record: ord-1654a4b1c29d46c58296fb28590760c0
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07915424B2

Reaction notes

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