Lithium Hydroxide → 2-[4-Methoxy-3-(3-methyl-benzyloxymethyl)-benzoylamino]-indane-2-carboxylic acid

HRID 2405300Notes

Reaction equation

C[O:2][C:3]([C:5]1([NH:14][C:15](=[O:26])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([CH2:24][OH:25])[CH:17]=2)[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6]1)=[O:4].[H-].[Na+].Br[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[CH:32]=1.[OH-].[Li+]>CN(C=O)C.O1CCOCC1>[CH3:23][O:22][C:19]1[CH:20]=[CH:21][C:16]([C:15]([NH:14][C:5]2([C:3]([OH:2])=[O:4])[CH2:6][C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH2:13]2)=[O:26])=[CH:17][C:18]=1[CH2:24][O:25][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[CH:32]=1

Participants

Conditions

Temperature: 60 °C

Procedure

The compound of step 2 (50 mg, 0.14 mmol)) was dissolved in DMF (3 ml) and sodium hydride (60% dispersion in mineral oil, 6.2 mg, 0.15 mmol) was added followed by 1-bromomethyl-3-methyl-benzene (27 mg, 0.14 mmol). The mixture was stirred overnight. Then lithium hydroxide (1 M solution in water, 0.42 ml) and dioxane (1 ml) were added and the mixture heated to 60° C. for 1 h. The residue was partitioned between 2 N hydrochloric acid and EA and the aqueous phase was extracted with EA. The combined organic phases were dried over sodium sulfate and evaporated to dryness. The residue was purified by RP HPLC (water/ACN gradient) to yield 5 mg of the title compound.

Workup

customThe residue was partitioned between 2 N hydrochloric acid and EA
extractionthe aqueous phase was extracted with EA
dry with materialThe combined organic phases were dried over sodium sulfate
customevaporated to dryness
customThe residue was purified by RP HPLC (water/ACN gradient)

Sources & evidence

ORD record: ord-7dadeecf80854e8fadf05d73cb5e50ae
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802720B2

Reaction notes

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