3-Bromo-4-methoxybenzoic acid → 2-(3-Bromo-4-methoxy-benzoylamino)-indane-2-carboxylic acid methyl ester

HRID 521484Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[C:5]([OH:7])=O.Cl.[CH3:14][O:15][C:16]([C:18]1([NH2:27])[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19]1)=[O:17]>S(Cl)(Cl)=O.C(Cl)Cl>[CH3:14][O:15][C:16]([C:18]1([NH:27][C:5](=[O:7])[C:4]2[CH:8]=[CH:9][C:10]([O:11][CH3:12])=[C:2]([Br:1])[CH:3]=2)[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19]1)=[O:17]

Participants

Conditions

Temperature: 60 °C

Procedure

3-Bromo-4-methoxybenzoic acid (22.8 g, 98.8 mmol) was dissolved in thionyl chloride (42 ml) and stirred at 60° C. for 30 min. The volatiles were evaporated in vacuo and the residue was stripped with dioxane. The obtained acid chloride was dissolved in DCM (50 ml). 2-Amino-indane-2-carboxylic acid methyl ester hydrochloride (15.0 g, 65.9 mmol) was suspended in DCM (100 ml), EDIA (10.2 g, 79.1 mmol) was added, the mixture was cooled in an ice bath, and the solution of the acid chloride was slowly added. The mixture was stirred overnight at room temperature and evaporated to dryness. The residue was purified by silica gel chromatography (DCM/methanol gradient) and subsequent crystallization from EA to give 21.8 g of the title compound.

Workup

customThe volatiles were evaporated in vacuo
dissolutionThe obtained acid chloride was dissolved in DCM (50 ml)
additionEDIA (10.2 g, 79.1 mmol) was added
temperaturethe mixture was cooled in an ice bath
stirringThe mixture was stirred overnight at room temperature
customevaporated to dryness
customThe residue was purified by silica gel chromatography (DCM/methanol gradient) and subsequent crystallization from EA

Sources & evidence

ORD record: ord-30e0985f63e94214b75c8d1c2a4714ff
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328071B2

Reaction notes

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