Hydrochloric Acid → HCID 178467323, compound

HRID 1912305Notes

Reaction equation

C[O-].[Na+].C(O[C:7](=[O:19])[CH:8]([O:16][CH2:17][CH3:18])[C:9](=O)[C:10]([O:12][CH2:13]C)=[O:11])C.Cl.[Cl:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([NH2:28])=[NH:27])=[C:24]([F:31])[C:23]=1[O:32][CH3:33].Cl>CO>[CH3:13][O:12][C:10]([C:9]1[C:8]([O:16][CH2:17][CH3:18])=[C:7]([OH:19])[N:27]=[C:26]([C:25]2[CH:29]=[CH:30][C:22]([Cl:21])=[C:23]([O:32][CH3:33])[C:24]=2[F:31])[N:28]=1)=[O:11]

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium methoxide (12 mL, 62.74 mmol) was added dropwise to a solution of 2-ethoxy-3-oxo-succinic acid diethyl ester (9.7 g of 75% purity, 31.37 mol), 4-chloro-2-fluoro-3-methoxybenzamidine hydrochloride (5 g, 20.91 mol) and MeOH (24 mL). The reaction was allowed to stir for 1 hour. The reaction was cooled to 0° C. and 1 N HCl was added to acidify the reaction. The reaction was extracted with ethyl acetate thrice. The organic extracts were combined, washed with brine, dried, filtered and concentrated. The product was purified by flash chromatography on silica gel (0-50% EtOAc/hexane) the recrystallized from dichloromethane/hexane to give a white solid (623 mg, 8% yield): mp 173-175° C.: 1H NMR (CDCl3) δ 11.28 (br s, 1H), 7.78 (dd, 1H), 7.31 (dd, 1H), 4.35 (q, 2H), 4.02 (s, 3H), 3.98 (s, 3H), 1.38 (t, 3H).

Workup

customthe reaction
extractionThe reaction was extracted with ethyl acetate thrice
washwashed with brine
customdried
filtrationfiltered
concentrationconcentrated
customThe product was purified by flash chromatography on silica gel (0-50% EtOAc/hexane) the
customrecrystallized from dichloromethane/hexane

Sources & evidence

ORD record: ord-adaba6527b2540fdb85f49ca245f8af5
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08609592B2

Reaction notes

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