Ammonia → Methyl 4-(2-(2-aminoacetamido)thiophene-3-carbonyl)benzoate

HRID 1946652Notes

Reaction equation

[NH2:1][C:2]1[S:3][CH:4]=[CH:5][C:6]=1[C:7]([C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=1)=[O:8].[I-].[Na+].C(=O)=O.[CH3:24][C:25](C)=[O:26].[NH3:28]>O1CCCC1>[NH2:28][CH2:24][C:25]([NH:1][C:2]1[S:3][CH:4]=[CH:5][C:6]=1[C:7]([C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=1)=[O:8])=[O:26]

Participants

Conditions

Temperature: -78 °C

Procedure

In a 100 mL round-bottomed flask was dissolved title compound 491 (1 g, 2.96 mmol) and sodium iodide (0.533 g, 3.55 mmol) in tetrahydrofuran (20 mL) to give a yellow suspension. The mixture was heated at reflux for 2 hours. The mixture was cooled to −78° C. A Dewar-type condenser was attached and filled with dry ice/acetone. Ammonia was introduced as a gas and about 30 mL was condensed into the flask. The reaction mixture was left to warm up to room temperature over the weekend. The solvent was removed in vacuo and the residue was purified via ISCO (50-100% EtOAc/Hexanes; 40 g silica gel column) to obtain product as a tan powder. The solid was purified by suspending it in 1:1 dichloromethane/ether and filtering to afford title compound 492 (265 mg, 28%) as a tan powder which was sufficiently pure for the next step. MS (m/z): 319.3 (M+H).

Workup

customto give a yellow suspension
temperatureThe mixture was heated
temperatureat reflux for 2 hours
customcondensed into the flask
waitThe reaction mixture was left
temperatureto warm up to room temperature over the weekend
customThe solvent was removed in vacuo
customthe residue was purified via ISCO (50-100% EtOAc/Hexanes; 40 g silica gel column)
customto obtain product as a tan powder
customThe solid was purified
filtrationfiltering

Sources & evidence

ORD record: ord-823085a3197549a9a36ef48fb574437c
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399452B2

Reaction notes

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