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

HRID 657968Notes

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-272a605e8082482ea18f2ff8cb079569
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08076336B2

Reaction notes

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