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

HRID 521532Notes

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-9145fc88b24a42a09654f6884b3f72b5
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328071B2

Reaction notes

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