Hydrochloric Acid → 1-((1R,2R)-2-Methyl-cyclohexyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid

HRID 1750235Notes

Reaction equation

C[O:2][C:3](=[O:27])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C@@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]2[CH3:17])=[C:6]([NH:18][C:19](=O)[CH2:20][C:21]2[S:22][CH:23]=[CH:24][CH:25]=2)[CH:5]=1.Cl.O>O1CCOCC1>[CH3:17][C@@H:12]1[CH2:13][CH2:14][CH2:15][CH2:16][C@H:11]1[N:10]1[C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:2])=[O:27])=[CH:5][C:6]=2[N:18]=[C:19]1[CH2:20][C:21]1[S:22][CH:23]=[CH:24][CH:25]=1

Participants

Conditions

Temperature: 130 °C

Procedure

To 8.32 g 4-((1R,2R)-2-Methyl-cyclohexylamino)-3-(2-thiophen-2-yl-acetylamino)-benzoic acid methyl ester were added 40 ml of 4M hydrochloric acid in dioxane and the mixture was heated in four portions in a microwave reactor to 130° C. for 20 min. 2 ml of water were added to each vial and the reactions were heated to 130° C. for 40 min. The reactions were then combined and concentrated and the pH was adjusted to 6 by addition of saturated aqueous sodium bicarbonate. The resulting mixture was extracted with ethyl acetate twice. The combined organic layers were dried over sodium sulphate and concentrated. The product precipitated upon treatment with diisopropylether and 5.65 g (76%) of 1-((1R,2R)-2-Methyl-cyclohexyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carboxylic acid were obtained.

Workup

temperaturewere heated to 130° C. for 40 min
concentrationconcentrated
additionthe pH was adjusted to 6 by addition of saturated aqueous sodium bicarbonate
extractionThe resulting mixture was extracted with ethyl acetate twice
dry with materialThe combined organic layers were dried over sodium sulphate
concentrationconcentrated
customThe product precipitated upon treatment with diisopropylether

Sources & evidence

ORD record: ord-1ee9044cfad348ef85f45c0fd38e15f6
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09156796B2

Reaction notes

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