Water → Methyl 4-(2-aminothiophene-3-carbonyl)benzoate

HRID 1946651Notes

Reaction equation

C(N(CC)CC)C.[C:8]([CH2:10][C:11]([C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=1)=[O:12])#[N:9].[S:23]1CC(O)S[CH2:25][CH:24]1O.O>CN(C)C=O.C(O)(=O)C.C(OCC)(=O)C>[NH2:9][C:8]1[S:23][CH:24]=[CH:25][C:10]=1[C:11]([C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=1)=[O:12]

Participants

Conditions

Temperature: 60 °C

Procedure

Triethylamine (1.331 mL, 9.55 mmol) was added with stirring to a solution of methyl 4-(2-cyanoacetyl)benzoate (4.85 g, 23.87 mmol) and 1,4-dithiane-2,5-diol (1.817 g, 11.93 mmol) in dimethylformamide (10 mL), to give a yellow solution. After 15 min, the solution was heated to 60° C. for 2 hours and stirred at room temperature overnight. Water (50 mL), ethyl acetate (50 mL), and glacial acetic acid (ca. 1-3 mL) were added to the oily residue until the organic layer became clear. After separation of the organic layer and further extraction of the aqueous layer with ethyl acetate (50 mL), the combined organic layers were washed subsequently with 5% aqueous NaHCO3 and H2O, dried over anhydrous MgSO4. The solvent was removed and the residue was purified via ISCO (0-50% EtOAc/Hexanes; 80 g silica gel column) to afford title compound 491 (3.7 g, 59%) as a yellow solid. MS (m/z): 357.4 (M+H).

Workup

customto give a yellow solution
customAfter separation of the organic layer and further extraction of the aqueous layer with ethyl acetate (50 mL)
washthe combined organic layers were washed subsequently with 5% aqueous NaHCO3 and H2O
dry with materialdried over anhydrous MgSO4
customThe solvent was removed
customthe residue was purified via ISCO (0-50% EtOAc/Hexanes; 80 g silica gel column)

Sources & evidence

ORD record: ord-188fba0a13b84ced9dc200b61fb372c4
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399452B2

Reaction notes

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