Ethyl 3-(trimethylsilyl)propynoate → Methyl 3-[1-(6-chloropyridazin-3-yl)-2-oxo-4-(trimethylsilyl)but-3-yn-1-yl]-4-methoxybenzoate

HRID 1454955Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[N:6][C:5]([CH2:8][C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][C:18]=2[O:19][CH3:20])[C:12]([O:14][CH3:15])=[O:13])=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:31][Si:32]([CH3:41])([CH3:40])[C:33]#[C:34][C:35](OCC)=[O:36]>C1COCC1>[Cl:1][C:2]1[N:7]=[N:6][C:5]([CH:8]([C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][C:18]=2[O:19][CH3:20])[C:12]([O:14][CH3:15])=[O:13])[C:35](=[O:36])[C:34]#[C:33][Si:32]([CH3:41])([CH3:40])[CH3:31])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of methyl 3-[(6-chloropyridazin-3-yl)methyl]-4-methoxybenzoate (10.03 g, 34.2 mmol) in THF (400 mL) was added LHMDS (100 mL, 1M solution in THF) and ethyl 3-(trimethylsilyl)propynoate (6.66 mL, 35.5 mmol) at −78° C. The reaction was warmed to 0° C. and stirred for 0.5 hr until the reaction was complete by LCMS analysis. The reaction was quenched with aqueous NH4Cl and extracted with ethyl acetate. The combined organic layers were washed with 0.5 N HCl, brine, dried over MgSO4, and condensed in vacuo to yield an oil. The crude material was purified via silica gel chromatography (CH2Cl2) to yield the title compound.

Workup

customThe reaction was quenched with aqueous NH4Cl
extractionextracted with ethyl acetate
washThe combined organic layers were washed with 0.5 N HCl, brine
dry with materialdried over MgSO4, and condensed in vacuo
customto yield an oil
customThe crude material was purified via silica gel chromatography (CH2Cl2)

Sources & evidence

ORD record: ord-0da6cc5dba5a4bcbbc4969e7a8ac72c1
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07482345B2

Reaction notes

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