Potassium Carbonate → 3-((R)-3-Cyclohexyl-5-oxo-morpholin-4-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

HRID 579170Notes

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([CH:29]2[NH:34][C:33](=[O:35])[CH2:32][O: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][O:31][CH2:30][C@H:29]1[CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)=[O:4]

Participants

Conditions

Temperature: 110 °C

Procedure

A heavy wall flask was charged with trans-cyclohexane diamine (623 mg, 5.5 mmol, 0.5 equiv), 3-bromo-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (4.27 g, 14.2 mmol, 1.3 equiv), K2CO3 (3.02 g, 21.8 mmol, 2.0 equiv), CuI (1.04 g, 5.5 mmol, 0.5 equiv), 5-cyclohexyl-morpholin-3-one (2.0 g, 10.9 mmol, 1.0 equiv) and 1,4-dioxane (10.0 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, EtOAc/heptane 50% to give product 2.8 g (yield 50%).

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, EtOAc/heptane 50%

Sources & evidence

ORD record: ord-d474782ec04e441bbe8a98c2c4148c4d
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040690B2

Reaction notes

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