tert-Butyldimethylsilyl chloride → 2-(T-Butyldimethylsilyloxy)-4-bromoanisole

HRID 2378164Notes

Reaction equation

HRID 2378164 reaction equation
C(N(C(C)C)C(C)C)C.[Br:10][C:11]1[CH:12]=[CH:13][C:14]([O:18][CH3:19])=[C:15]([OH:17])[CH:16]=1.[C:20]([Si:24](Cl)([CH3:26])[CH3:25])([CH3:23])([CH3:22])[CH3:21].C([O-])(O)=O.[Na+]>CN(C=O)C.CCOCC.O>[Br:10][C:11]1[CH:12]=[CH:13][C:14]([O:18][CH3:19])=[C:15]([CH:16]=1)[O:17][Si:24]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:26])[CH3:25]

Participants

8

Reactant 4

HCID 28928tert-Butyldimethylsilyl chlorideHCID 81531DiisopropylethylamineHCID 1422285-Bromo-2-methoxyphenolHCID 516892Sodium Bicarbonate

Product 1

HCID 109800492-(T-Butyldimethylsilyloxy)-4-bromoanisoleYield 99%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

Ethyldiisopropylamine (1.72 ml, 9.85 mmol) was added to a solution of 5-bromo-2-methoxy-phenol (0.80 g, 3.94 mmol) in DMF (10 ml) at rt. The clear, colorless solution was stirred for 5 min. followed by addition of tert-butylchlorodimethylsilane (0.71 g, 4.73 mmol). The reaction was complete in about two hours. Distilled water (˜6 ml) was added to the clear solution, stirred for 10 min., added ether (50 ml) and sat. NaHCO3 (10 ml), stirred for 30 min. The ether portion was separated and the aqueous phase was extracted with ether (2×50 ml). The combined ether phases were washed with water (100 ml), brine (60 ml), dried over MgSO4, filtered and concentrated to an oil, which was further purified by flash column chromatography [100% hexane with 0.5% triethylamine gradient to 30% EtOAc in hexane with 0.5% Et3N] to give (5-bromo-2-methoxy-phenoxy)-tert-butyl-dimethyl-silane as an oil (0.59 g, 99%), HPLC purity 99.5% at 1.43 min. (90/10 ACN/0.1% H3PO4): 1H NMR (DMSO-d6) δ 7.04-6.97(m, 2H, Ar), 6.71 (d, J=8 Hz, Ar), 3.78 (s, 3H, single OCH3), 0.99 (s, 9H, 3OCH3), 0.16 (s, 6H, 2OCH3). The product was carried over to the next step.

Workup

  1. waitThe reaction was complete in about two hours
  2. stirringstirred for 10 min.
  3. stirringstirred for 30 min
  4. customThe ether portion was separated
  5. extractionthe aqueous phase was extracted with ether (2×50 ml)
  6. washThe combined ether phases were washed with water (100 ml), brine (60 ml)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to an oil, which
  10. customwas further purified by flash column chromatography [100% hexane with 0.5% triethylamine gradient to 30% EtOAc in hexane with 0.5% Et3N]

Sources & evidence

ORD record
ord-b296d553ff9b4083b138e89cd5e86406
Source dataset
uspto-grants-2008_12
Patent number
US07470723B2

Reaction notes

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