Pyridine, 2-bromo-5-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]- → 5-(tert-Butyldimethylsilyloxymethyl)-2-(3-methyl-butyryl)-pyridine

HRID 911715Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])=[CH:4][N:3]=1.[Li]CCCC.CON(C)[C:25](=[O:30])[CH2:26][CH:27]([CH3:29])[CH3:28]>C1COCC1>[Si:10]([O:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:25](=[O:30])[CH2:26][CH:27]([CH3:29])[CH3:28])=[N:3][CH:4]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

Conditions

Temperature: -78 °C

Procedure

Dissolve 2-bromo-5-(tert-butyldimethylsilyloxymethyl)pyridine (1.99 g, 6.583 mmol, prepared by following the procedure described in J. Org. Chem. 2004, 69, 250-262) in anhydrous THF (20 mL). Cool the solution to −78° C., add n-BuLi (4.32 mL, 6.912 mmol, 1.6M solution in hexane) and stir at this temperature for 40 min. Add slowly a solution of N-methoxy-N-methyl-3-methyl-butyramide (0.955 g, 6.583 mmol) in anhydrous THF (5 mL). Stir the mixture for 2 h at −78° C. and then allow the mixture to warm to room temperature. Add brine and extract the aqueous layer twice with EtOAc. Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane and hexane/EtOAc (19:1) to give the desired intermediate as yellow oil (890 mg, 44%). GC-MS m/z: 307 (M+).

Workup

customprepared
stirringStir the mixture for 2 h at −78° C.
temperatureto warm to room temperature
extractionAdd brine and extract the aqueous layer twice with EtOAc
dry with materialDry the combined organic extracts over Na2SO4
filtrationfilter
concentrationconcentrate in vacuo
customPurify the crude mixture by chromatography on silica gel eluting with hexane and hexane/EtOAc (19:1)

Sources & evidence

ORD record: ord-baa84696552b4beaab249ebdcd68b33e
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022062B2

Reaction notes

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