HCID 89740097, compound → HCID 89740020, compound

HRID 1527064Notes

Reaction equation

[CH3:1][C:2]1[N:3]([CH:18]([C:20](=[O:22])[CH3:21])[CH3:19])[C:4]2[C:9]([C:10]=1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.[CH3:23][Li]>>[OH:22][C:20]([CH3:23])([CH3:21])[CH:18]([N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:10]([C:11]([O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:12])=[C:2]1[CH3:1])[CH3:19]

Participants

Reactant 2

HCID 89740097HCID 89740097, compound

HCID 178418348HCID 178418348, compound

Product 1

HCID 89740020HCID 89740020, compound

Conditions

Temperature: -78 °C

Procedure

A 50 mL round bottom flask was charged with (±)-tert-butyl 2-methyl-1-(3-oxobutan-2-yl)-1H-indole-3-carboxylate (0.2441 g, 0.810 mmol), vac/purged with N2, diluted with THF (5 mL) and cooled to −78° C. Methyllithium (0.648 ml, 0.972 mmol) was then added slowly, drop-wise, and the solution was allowed to slowly warm to ambient temperature. The reaction was then quenched with 1N HCl, extracted with EtOAc. The org layer was washed with water then brine, dried over Na2SO4, filtered, concentrated, purified by column chromatography using 10% EtOAc in Hex (10 CV), 15% (10 CV) to elute (±)-tert-butyl 1-(3-hydroxy-3-methylbutan-2-yl)-2-methyl-1H-indole-3-carboxylate (157.2 mg, 61.1%). LRMS (M+H+) m/z: calcd 318.42. found 318.2.

Workup

customvac/purged with N2
additiondiluted with THF (5 mL)
temperatureto slowly warm to ambient temperature
customThe reaction was then quenched with 1N HCl
extractionextracted with EtOAc
washThe org layer was washed with water
dry with materialbrine, dried over Na2SO4
filtrationfiltered
concentrationconcentrated
custompurified by column chromatography
washto elute (±)-tert-butyl 1-(3-hydroxy-3-methylbutan-2-yl)-2-methyl-1H-indole-3-carboxylate (157.2 mg, 61.1%)

Sources & evidence

ORD record: ord-e95963354cef49d9b0cb221c123840d9
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085583B2

Reaction notes

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