Morpholine → Ethyl 4-cyano-3-iodo-5-morpholin-4-ylthiophene-2-carboxylate

HRID 2402108Notes

Reaction equation

[C:1]([C:3]1[C:4]([I:17])=[C:5]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[S:6][C:7]=1S(C)(=O)=O)#[N:2].O1CCOCC1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1>O>[C:1]([C:3]1[C:4]([I:17])=[C:5]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[S:6][C:7]=1[N:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1)#[N:2]

Participants

Conditions

Temperature: 90 °C

Procedure

To a 500 mL RBF containing ethyl 4-cyano-3-iodo-5-(methylsulfonyl)thiophene-2-carboxylate (17.20 g, 44.65 mmol, prepared as in WO 2009154741) was added anhydrous 1,4-dioxane (172.0 mL, 2204 mmol). To the resulting suspension was added morpholine (8.177 mL, 93.77 mmol). A reflux condenser was attached and the pink/orange heterogeneous suspension was heated to bath temp 90° C. and allowed to stir. Shortly after heating began, reaction mixture became a cherry red, homogenous solution. Reaction was stirred for 16 hours at 90° C. The reaction was then cooled to room temperature and diluted with water (100 mL). Mixture was filtered, and the solid was dried for in vacuo at 40° C. for 5 days to afford ethyl 4-cyano-3-iodo-5-morpholin-4-ylthiophene-2-carboxylate (14.3 grams, 82% yield). LCMS: (FA) ES+ 393; 1H NMR (400 MHz, DMSO) δ 4.24 (q, J=7.1, 2H), 3.78-3.70 (m, 4H), 3.63-3.57 (m, 4H), 1.26 (t, J=7.1, 3H).

Workup

customA reflux condenser was attached
temperatureShortly after heating
customreaction mixture
customReaction
stirringwas stirred for 16 hours at 90° C
temperatureThe reaction was then cooled to room temperature
filtrationMixture was filtered
customthe solid was dried for in vacuo at 40° C. for 5 days

Sources & evidence

ORD record: ord-785cd39d018947fc8959fd9273754e7a
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08796271B2

Reaction notes

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