Isobutylene → 3-tert-Butylamino-5-phenyl-thiophene-2-carboxylic acid methyl ester

HRID 2193919Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:8][C:9]=1[NH2:10])=[O:4].[CH2:17]=[C:18]([CH3:20])[CH3:19]>S(=O)(=O)(O)O.O1CCOCC1.C(Cl)(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:8][C:9]=1[NH:10][C:18]([CH3:20])([CH3:19])[CH3:17])=[O:4]

Participants

Conditions

Temperature: -78 °C

Procedure

Concentrated sulfuric acid (10 drop) was added to a solution of 3-Amino-5-phenyl-thiophene-2-carboxylic acid methyl ester (500 mg, 2.15 mmol) in 20 ml of dioxane/chloroform (2:3) in a sealed tube. After cooling the solution at −78° C., put 20 ml of isobutene gas. The sealed tube was closed and then the reaction mixture was stirred for 6 days at 60° C. The solvent was removed and then partitioned between 15 ml of sat. Na2CO3 solution and 15 ml of EtOAc. The organic layer was separated, the aqueous phase was washed twice with ethyl acetate and the combined ethyl acetate layer was dried (MgSO4), concentrated and the residue was purified by flash chromatography (5% EtOAc/Hexane) to obtain 385 mg (62%) of 3-tert-Butylamino-5-phenyl-thiophene-2-carboxylic acid methyl ester. NMR 1H (CDCl3, 400 MHz): 7.65 ppm (d, 2H, Haro); 7.44-7.38 ppm (m, 3H, Haro); 7.07 ppm (s, 1H, Haro); 3.86 ppm (s, 3H); 1.48 ppm (s, 9H).

Workup

customThe sealed tube was closed
customThe solvent was removed
custompartitioned between 15 ml of sat. Na2CO3 solution and 15 ml of EtOAc
customThe organic layer was separated
washthe aqueous phase was washed twice with ethyl acetate
dry with materialthe combined ethyl acetate layer was dried (MgSO4)
concentrationconcentrated
customthe residue was purified by flash chromatography (5% EtOAc/Hexane)

Sources & evidence

ORD record: ord-7e2547a8a47741248c84d8899ece356d
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329924B2

Reaction notes

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