Imidazole → 4-[2-(t-Butyldimethylsilanyloxy)ethoxymethyl]benzoic acid methyl ester

HRID 1751839Notes

Reaction equation

HRID 1751839 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][O:11][CH2:12][CH2:13][OH:14])=[CH:6][CH:5]=1.[Si:16](Cl)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17].N1C=CN=C1.CCCCC>CN(C=O)C.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:5]=[CH:6][C:7]([CH2:10][O:11][CH2:12][CH2:13][O:14][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 795Imidazole2×HCID 8003PentaneHCID 28928tert-Butyldimethylsilyl chloride2×HCID 23344083Methyl 4-((2-hydroxyethoxy)methyl)benzoate

Product 1

HCID 596786884-[2-(t-Butyldimethylsilanyloxy)ethoxymethyl]benzoic acid methyl esterYield 79.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the product of Example 8A (500 mg, 2.334 mmol) in DMF (23 mL) was added tert-butyldimethylsilyl chloride (528 mg, 3.501 mmol) and imidazole (238 mg, 3.501). The reaction was stirred at room temperature for 5 hours under nitrogen atmosphere, monitoring by TLC (3:1 pentane:ethyl acetate). Another 0.5 eq. portion of tert-butyldimethylsilyl chloride (176 mg) and imidazole (79 mg) were added and the resultant mixture stirred at room temperature overnight. The majority of the starting material was consumed in 16 hours, as indicated by thin layer chromatography. The reaction was diluted with water and extracted with ethyl acetate (2 times). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to obtain a crude oil which was purified by passage through thick pad of silica gel (3:1 pentane:ethyl acetate) to obtain the product as a clear oil (602 mg). 1H NMR (600 MHz, CDCl3): 8.00 (d, 2H, J=8.3 Hz), 7.40 (d, 2H, J=8.5 Hz), 4.62 (s, 2H), 3.90 (s, 3H), 0.90 (s, 9H), 0.06 (s, 6H).

Workup

  1. customThe majority of the starting material was consumed in 16 hours
  2. additionThe reaction was diluted with water
  3. extractionextracted with ethyl acetate (2 times)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto obtain a crude oil which
  8. customwas purified by passage through thick pad of silica gel (3:1 pentane:ethyl acetate)

Sources & evidence

ORD record
ord-811ad683cc1044bfacf3714afdc60e6e
Source dataset
uspto-grants-2015_10
Patent number
US09161997B2

Reaction notes

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