N-Methoxy-N-methylpropionamide → 1-(2-((tert-Butyldimethylsilyloxy)methyl)-1-methyl-1H-indol-5-yl)propan-1-one

HRID 1481752Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[C:6]([CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])=[CH:5]2.[Li]CCCC.CON(C)[C:29](=[O:32])[CH2:30][CH3:31]>C1COCC1>[Si:14]([O:13][CH2:12][C:6]1[N:7]([CH3:11])[C:8]2[C:4]([CH:5]=1)=[CH:3][C:2]([C:29](=[O:32])[CH2:30][CH3:31])=[CH:10][CH:9]=2)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

Conditions

Temperature: -78 °C

Procedure

To a stirred solution of 5-bromo-2-((tert-butyldimethylsilyloxy)methyl)-1-methyl-1H-indole (3.76 g, 10.6 mmol), prepared according to procedure described in Example 39 Step 3, in THF (15 mL) was added n-BuLi (2.5 M solution in hexanes, 5.1 mL, 12.7 mmol, 1.2 eq) at −78° C. dropwise. The mixture was stirred for 30 min at −78° C. before a solution of N-methoxy-N-methylpropionamide (1.49 g, 12.7 mmol, 1.2 eq) in THF (5 mL) was added. After stirred at −78° C. for 10 min, the reaction was quenched with saturated aqueous NH4Cl solution. The resulting mixture was extracted by ether (3×30 mL) and combined organic layers were dried over Na2SO4. The crude product was purified by flash chromatography (0-10% EtOAc in hexanes) to give the title compound (2.70 g, 77%).

Workup

additionwas added
customthe reaction was quenched with saturated aqueous NH4Cl solution
extractionThe resulting mixture was extracted by ether (3×30 mL)
dry with materialwere dried over Na2SO4
customThe crude product was purified by flash chromatography (0-10% EtOAc in hexanes)

Sources & evidence

ORD record: ord-d2140aa71d614955934064ad5a25c1b4
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409905B2

Reaction notes

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