Ethyl 3-(trimethylsilyl)propynoate → 1-(6-Chloropyridazin-3-yl)-1-(2,6-difluorophenyl)-4-(trimethylsilyl)but-3-yn-2-one

HRID 1454963Notes

Reaction equation

[Cl:1][C:2]1[N:3]=[N:4][C:5]([CH2:8][C:9]2[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=2[F:16])=[CH:6][CH:7]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:27][Si:28]([CH3:37])([CH3:36])[C:29]#[C:30][C:31](OCC)=[O:32]>C1COCC1>[Cl:1][C:2]1[N:3]=[N:4][C:5]([CH:8]([C:9]2[C:10]([F:16])=[CH:11][CH:12]=[CH:13][C:14]=2[F:15])[C:31](=[O:32])[C:30]#[C:29][Si:28]([CH3:37])([CH3:36])[CH3:27])=[CH:6][CH:7]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 3-chloro-6-(2,6-difluorobenzyl)pyridazine (5.7 g, 23.7 mmol) in THF (300 mL) was added LHMDS (71.2 mL, 71.2 mmol, 1M solution in THF) via cannula at −78° C. After stirring for 0.5 hr at −78° C., ethyl 3-(trimethylsilyl)propynoate (6.66 mL, 35.5 mmol) was added. The reaction was allowed to warm from −78° C. to −10° C. over 3 hours. The reaction was known to be complete by LCMS analysis; and then quenched with aqueous NH4Cl, extracted with ethyl acetate. The organic layers were combined, washed with 0.5 N HCl, water, brine, dried over MgSO4, and condensed in vacuo to yield an oil. The crude material was purified via silica gel chromatography (EtOAc/Hex) to yield the title compound (9.6 g).

Workup

temperatureto warm from −78° C. to −10° C. over 3 hours
customand then quenched with aqueous NH4Cl
extractionextracted with ethyl acetate
washwashed with 0.5 N HCl, water, brine
dry with materialdried over MgSO4, and condensed in vacuo
customto yield an oil
customThe crude material was purified via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record: ord-b7b5a278d4664b3885bc63fbdbbad84f
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07482345B2

Reaction notes

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