Acetic Acid → Fumarate

HRID 416511Notes

Reaction equation

[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([N:10]([CH2:25][CH2:26][CH2:27][O:28][CH:29]2[CH2:34]CCC[O:30]2)[S:11]([CH2:14][CH2:15][NH:16][C:17]([C:19]2[S:20][C:21]([Cl:24])=[CH:22][CH:23]=2)=[O:18])(=[O:13])=[O:12])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[C:35]([OH:38])(=[O:37])[CH3:36]>C1COCC1.O.C(O)(=O)/C=C/C(O)=O>[OH:28][CH2:27][CH2:26][CH2:25][N:10]([CH:7]1[CH2:6][CH2:5][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:9][CH2:8]1)[S:11]([CH2:14][CH2:15][NH:16][C:17]([C:19]1[S:20][C:21]([Cl:24])=[CH:22][CH:23]=1)=[O:18])(=[O:12])=[O:13].[C:29]([O-:30])(=[O:28])/[CH:34]=[CH:36]/[C:35]([O-:38])=[O:37]

Participants

Conditions

Temperature: 60 °C

Procedure

220 mg (0.38 mmol) 5-Chloro-thiophene-2-carboxylic acid (2-{(1-isopropyl-piperidin-4-yl)-[3-(tetrahydro-pyran-2-yloxy)-propyl]-sulfamoyl}-ethyl)-amide were dissolved in a mixture of 4 ml THF, 8 ml conc. acetic acid and 2 ml water. The resulting mixture was stirred for 8 h at 60° C., concentrated under reduced pressure and purified by preparative RP-HPLC (CH3CN/H2O gradient+0.1% TFA). The product was taken up in dichloromethane and treated with a saturated NaHCO3-solution. After phase separation the organic phase was concentrated and the resulting residue was dissolved in water containing 1 equiv. of fumaric acid. Lyophilisation gave the title compound as its fumarate in form of a colorless amorphous material.

Workup

concentrationconcentrated under reduced pressure
custompurified by preparative RP-HPLC (CH3CN/H2O gradient+0.1% TFA)
additiontreated with a saturated NaHCO3-solution
customAfter phase separation the organic phase
concentrationwas concentrated

Sources & evidence

ORD record: ord-4e5d5f52a9e54776b1dde07c9ebdf502
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088925B2

Reaction notes

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