Lithium Hexamethyldisilazide → 1-[3-Tert-butyl-5-(3-hydroxypropoxy)phenyl]ethanone

HRID 532381Notes

Reaction equation

[C:1]([C:5]1[CH:6]=[C:7]([CH:14]=[C:15]([O:17][CH2:18][CH2:19][CH2:20][O:21]C2CCCCO2)[CH:16]=1)[C:8](N(OC)C)=[O:9])([CH3:4])([CH3:3])[CH3:2].[CH3:28][Si]([N-][Si](C)(C)C)(C)C.[Li+].C[Mg]Br>C1COCC1>[C:1]([C:5]1[CH:6]=[C:7]([C:8](=[O:9])[CH3:28])[CH:14]=[C:15]([O:17][CH2:18][CH2:19][CH2:20][OH:21])[CH:16]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 0 °C

Procedure

3-tert-Butyl-N-methoxy-N-methyl-5-[3-(tetrahydropyran-2-yloxy)propoxy]benzamide (O3.059; 5.49 g) was dissolved in THF (100 ml), cooled to 0° C. and admixed with lithium bis(trimethylsilyl)amide (14.47 ml, 1 M in MTB ether). After stirring at 0° C. for 30 min, methylmagnesium bromide (9.65 ml, 3 M in ether) was added dropwise. The cooling bath was removed and, after stirring at RT for 2 h, the mixture was diluted with water and extracted by shaking with EA. The EA phase was dried over magnesium sulfate, filtered and concentrated by rotary evaporation. The residue was purified using silica gel (200 g, n-heptane/EA 4:1). 3.4 g of the title compound were obtained.

Workup

customThe cooling bath was removed
stirringafter stirring at RT for 2 h
additionthe mixture was diluted with water
extractionextracted
stirringby shaking with EA
dry with materialThe EA phase was dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated by rotary evaporation
customThe residue was purified

Sources & evidence

ORD record: ord-17fb1971b98e4228825be3a86d1f2e3d
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853206B2

Reaction notes

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