5-(Chloromethyl)-1,2,3-trimethoxybenzene → HCID 18464751, compound

HRID 323305Notes

Reaction equation

HRID 323305 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][C:11]1([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:15][C:14](=[O:16])[NH:13][CH2:12]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:34][O:35][C:36]1[CH:37]=[C:38]([CH:41]=[C:42]([O:46][CH3:47])[C:43]=1[O:44][CH3:45])[CH2:39]Cl.C(OCC)(=O)C.CCCCCC>O1CCCC1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:47][O:46][C:42]1[CH:41]=[C:38]([CH:37]=[C:36]([O:35][CH3:34])[C:43]=1[O:44][CH3:45])[CH2:39][N:13]1[C:14](=[O:16])[CH2:15][C:11]([CH2:10][CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:12]1

Participants

7

Reactant 4

HCID 774485-(Chloromethyl)-1,2,3-trimethoxybenzeneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 18464945HCID 18464945, compoundHCID 21226206Ethyl acetate hexane

Product 1

HCID 18464751HCID 18464751, compound

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Combine 3-(2-(t-butyldimethylsilyloxy)ethyl)-3-(phenylmethyl)-5-oxopyrrolidine (0.13 g, 0.38 mmol) and tetrahydrofuran (2 mL). Cool to −78° C. using a dry-ice/acetone bath. Add a solution of potassium bis(trimethylsilyl)amide (0.76 mL, 0.5 M in toluene, 0.38 mmol). After 30 minutes, add a solution of 3,4,5-trimethoxybenzyl chloride (0.08 g, 0.38 mmol) in tetrahydrofuran (1 mL). Warm to ambient temperature and add tetrabutylammonium bromide (0.01 g). Heat to reflux. After 12 hours, cool the reaction mixture and partition between water and ethyl acetate. Separate the aqueous layer and extract twice with ethyl acetate. Dry the combined organic layers over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 1/4 ethyl acetate/hexane to give the title compound: Rf=0.43 (silica gel, 1/1 ethyl acetate/hexane).

Workup

  1. temperatureWarm to ambient temperature
  2. temperatureHeat to reflux
  3. waitAfter 12 hours
  4. temperaturecool the reaction mixture
  5. custompartition between water and ethyl acetate
  6. customSeparate the aqueous layer
  7. extractionextract twice with ethyl acetate
  8. dry with materialDry the combined organic layers over Na2SO4
  9. filtrationfilter
  10. concentrationconcentrate in vacuo
  11. customto obtain a residue

Sources & evidence

ORD record
ord-6f5c5e95521143a594ebc6a87c58c1b0
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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