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

HRID 579174Notes

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])[CH:32]([CH2:36][CH2:37][CH2:38][OH:39])[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[CH:29]([CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[CH2:30][O:31][C@H:32]([CH2:36][CH2:37][CH2:38][OH:39])[C:33]1=[O:35])=[O:4]

Participants

Conditions

Temperature: 110 °C

Procedure

A 10 mL heavy wall vial was charged with trans-cyclohexane diamine (11.8 mg, 0.10 mmol, 0.5 equiv), 3-bromo-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (125 mg, 0.41 mmol, 2.0 equiv), K2CO3 (57 mg, 0.41 mmol, 2.0 equiv), CuI (19.7 mg, 0.10 mmol, 0.5 equiv), 5-cyclohexyl-2-(3-hydroxy-propyl)-morpholin-3-one (50 mg, 0.21 mmol, 1.0 equiv) and 1,4-dioxane (0.5 mL). The mixture was flushed with N2 and stirred at 110° C. for 24 hours. The mixture was filtered through celite and the filtrate was concentrated under vacuum. The residue was purified by silica gel, EtOAc/heptane 30% to give product 10 mg (yield 10%).

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 30%

Sources & evidence

ORD record: ord-3b0663ab456a4a7f841d2feae1d8afff
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040690B2

Reaction notes

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