Methyl iodide → HCID 71003903, compound

HRID 2201760Notes

Reaction equation

C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:11]([CH:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([O:27][CH3:28])[CH:25]=2)[C:20](=[O:29])[N:19]1[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.I[CH3:38]>C1COCC1>[CH2:11]([C:18]1([CH3:38])[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([O:27][CH3:28])[CH:25]=2)[C:20](=[O:29])[N:19]1[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

Conditions

Temperature: -78 °C

Procedure

Lithium bis(trimethysilyl)amide (5.04 mL, 5.04 mmol, 1 M in THF) was added to a solution of the tert-butyl 3-benzyl-5-methoxy-1-oxoisoindoline-2-carboxylate (example 1.3, 890 mg, 2.52 mmol) in THF (8 mL) at −78° C. After stirring the solution at −78° C. for 1 hr, iodomethane (465 mg, 3.27 mmol) was added, this was stirred at −78° C. for 1.5 hours. LC/MS showed complete conversion. Quenched the reaction mixture with saturated NaCl solution, then extracted with ethyl acetate, the combined organic layer was washed 1× with saturated NaCl solution. The organic phase was dried on Na2SO4 and the solvent was evaporated. The residue was purified by flash-chromatography on silica gel with 25-40% ethyl acetate in hexane, 750 mg (2.04 mmol, 81%) of the product was obtained.

Workup

stirringthis was stirred at −78° C. for 1.5 hours
customQuenched the reaction mixture with saturated NaCl solution
extractionextracted with ethyl acetate
washthe combined organic layer was washed 1× with saturated NaCl solution
customThe organic phase was dried on Na2SO4
customthe solvent was evaporated
customThe residue was purified by flash-chromatography on silica gel with 25-40% ethyl acetate in hexane

Sources & evidence

ORD record: ord-c4b121a0f3ad44168158c2a1fdd59f57
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365512B2

Reaction notes

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