Cesium carbonate → 5-(3,3-Dimethyl-but-1-ynyl)-3-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-thiophene-2-carboxylic acid methyl ester

HRID 632551Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]#[C:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:8][C:9]=1I)=[O:4].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[O:69]1[C:73]2([CH2:78][CH2:77][CH:76]([NH2:79])[CH2:75][CH2:74]2)[O:72][CH2:71][CH2:70]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]#[C:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:8][C:9]=1[NH:79][CH:76]1[CH2:77][CH2:78][C:73]2([O:69][CH2:70][CH2:71][O:72]2)[CH2:74][CH2:75]1)=[O:4]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 5-(3,3-dimethyl-but-1-ynyl)-3-iodo-thiophene-2-carboxylic acid methyl ester (0.5 g, 1.5 mmol), palladium acetate (0.033 g, 0.15 mmol), BINAP (0.093 g, 0.15 mmol), cesium carbonate (0.733 g, 2.25 mmol) and 1,4-Dioxa-spiro[4.5]dec-8-ylamine (0.706 g, 4.5 mmol) in toluene (8 mL) was degassed with N2 then heated to 110° C. for 8 h. The reaction was diluted with ethyl acetate filtered through a Celite pad and purified by silica gel chromatography (0-40% hexane/ethylacetate) to give the title compound in 50% yield. MS (m/z): 378.1 [M+H]; HPLC retention time: 5.12 min (2-98% acetonitrile:water with 0.05% trifluoroacetic acid).

Workup

customwas degassed with N2
additionThe reaction was diluted with ethyl acetate
filtrationfiltered through a Celite pad
custompurified by silica gel chromatography (0-40% hexane/ethylacetate)

Sources & evidence

ORD record: ord-675588a394304eb59e671eebcae35b69
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321753B2

Reaction notes

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