4-Methylmorpholine → 5-Acetyl-N-methoxy-N-methylthiophene-2-carboxamide

HRID 1244155Notes

Reaction equation

[C:1]([C:4]1[S:8][C:7]([C:9]([OH:11])=O)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.[CH3:34][NH:35][O:36][CH3:37].CN1CCOCC1>CC(N(C)C)=O.O>[C:1]([C:4]1[S:8][C:7]([C:9]([N:35]([O:36][CH3:37])[CH3:34])=[O:11])=[CH:6][CH:5]=1)(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of 5-acetylthiophene-2-carboxylic acid (5 g, 0.0294 mol) in DMA (80 mL) was treated with EDCI (8.47 g, 0.044 mol), HOBt (3.97 g, 0.044 mol), N,O-dimethylhydroxylamine hydrochloride (5.7 g, 0.059 mol) and 4-methylmorpholine (16.14 mL, 0.147 mol). The resulting thick mixture was stirred at 25° C. for 16 h. Water (250 mL) was added and the mixture was extracted with 1:1 EtOAc/ether (2×200 mL). The combined extracts were washed with 1N HCl (150 mL), water (3×200 mL), saturated NaHCO3 (150 mL), and brine (150 mL); dried (Na2SO4); filtered; and evaporated to afford 5.4 g (86%) of the desired product. 1H NMR (300 MHz, DMSO-D6) δ ppm 2.58 (s, 3H) 3.31 (s, 3H) 3.78 (s, 3H) 7.85 (d, J=4.04 Hz, 1H) 7.92 (d, J=4.04 Hz, 1H); MS (DCI) 214 m/z (M+H)+.

Workup

extractionthe mixture was extracted with 1:1 EtOAc/ether (2×200 mL)
washThe combined extracts were washed with 1N HCl (150 mL), water (3×200 mL), saturated NaHCO3 (150 mL), and brine (150 mL)
dry with materialdried (Na2SO4)
filtrationfiltered
customand evaporated

Sources & evidence

ORD record: ord-9658dc63c7444e658c04b42c23b1df6b
Source dataset: uspto-grants-2006_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07119205B2

Reaction notes

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