Potassium Carbonate → 3-((S)-2-Cyclohexyl-6-oxo-piperidin-1-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

HRID 579183Notes

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]=1Br)=[O:4].C([O-])([O-])=O.[K+].[K+].[CH:23]1([C@H:29]2[NH:34][C:33](=[O:35])[CH2:32][CH2:31][CH2:30]2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>[Cu]I.O1CCOCC1>[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[N:34]1[C:33](=[O:35])[CH2:32][CH2:31][CH2:30][C@H:29]1[CH:23]1[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]1)=[O:4]

Participants

Conditions

Temperature: 110 °C

Procedure

To a 10 mL vial was added trans-cyclohexane diamine (283 mg, 2.5 mmol, 0.5 equiv), 3-Bromo-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (2.24 g, 7.4 mmol, 1.5 equiv), K2CO3 (1.37 g, 9.9 mmol, 2.0 equiv), CuI (473 mg, 2.5 mmol, 0.5 equiv), (S)-6-Cyclohexyl-piperidin-2-one (900 mg, 5.0 mmol, 1.0 equiv) and 1,4-dioxane (5.0 mL). The mixture was flushed with N2 and stirred at 110° C. for 48 hours. The mixture was filtered through Celite and the filtrate was concentrated under vacuum. The residue was purified by silica gel column chromatography, EtOAc/heptane 30% to give product 800 mg (yield 40%).

Workup

customThe mixture was flushed with N2
filtrationThe mixture was filtered through Celite
concentrationthe filtrate was concentrated under vacuum
customThe residue was purified by silica gel column chromatography, EtOAc/heptane 30%

Sources & evidence

ORD record: ord-2f7d16b92c3e493a9a111da90bbbbf6d
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040690B2

Reaction notes

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