3-Pyridinecarboxaldehyde → [4-(Tert-butyldimethylsilyloxymethyl)-phenyl]-pyridin-3-yl-methanol

HRID 911708

Reaction equation

[Si:1]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13](Br)=[CH:12][CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li]CCCC.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH:28]=[O:29])[CH:23]=1>C1COCC1>[Si:1]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([CH:28]([C:24]2[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=2)[OH:29])=[CH:12][CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: -78 °C

Procedure

Dissolve 4-(tert-butyldimethylsilyloxymethyl)bromobenzene (1 g, 3.319 mmol, prepared by following the procedure described in J. Am. Chem. Soc. 1995, 117, 704-714) in anhydrous THF (20 mL). Cool the solution to −78° C., add n-BuLi (4.149 mL, 6.638 mmol, 1.6M solution in hexane) and stir at this temperature for 1.5 h. Warm to −60° C., stir for an additional 30 min and add 3-pyridine carboxaldehyde. Allow the reaction mixture to warm gradually to room temperature and stir overnight. Add brine and extract with EtOAc. Dry the organic phase over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting sequentially with hexane and EtOAc to give the desired intermediate (380 mg, 35%). MS (ES+) m/z: 330 (M+H)*.

Workup

customprepared
temperatureWarm to −60° C.
stirringstir for an additional 30 min
temperatureto warm gradually to room temperature
stirringstir overnight
extractionAdd brine and extract with EtOAc
dry with materialDry the organic phase over Na2SO4
filtrationfilter
concentrationconcentrate in vacuo
customPurify the crude mixture by chromatography on silica gel eluting sequentially with hexane and EtOAc

Sources & evidence

ORD record: ord-072283dcc40a409990eb3aa9b8014da3
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022062B2

Linked notes

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