Tetrahydrofuran → alpha-trimethylsilylethoxymethyl-DL-tryptophan methyl ester

HRID 54860

Reaction equation

HRID 54860 reaction equation
[CH3:1][O:2][C:3]([CH:5]([NH2:16])[CH2:6][C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:9][CH:8]=1)=[O:4].C([N-]C(C)C)(C)C.[Li+].[CH3:25][Si:26]([CH2:29][CH2:30]OCCl)([CH3:28])[CH3:27].C1C[O:37][CH2:36]C1>>[CH3:1][O:2][C:3](=[O:4])[CH:5]([CH2:6][C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:9][CH:8]=1)[NH:16][CH2:36][O:37][CH:29]([Si:26]([CH3:25])([CH3:27])[CH3:28])[CH3:30]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 122205Methyl DL-tryptophanateHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 2724682Lithium diisopropylamide

Product 1

HCID 86747504alpha-trimethylsilylethoxymethyl-DL-tryptophan methyl esterYield 44%

Conditions

Temperature
-10 °C

Procedure

A solution of DL-tryptophan methyl esterbenzaldimine (4.0 g, 13 mmol) in 30 mL THF was added over 15 minutes to a mixture of 20.2 mL lithiumdiisopropylamide (10% suspension in hexan) and 70 mL dry THF, cooled to -10° C. under nitrogen atmosphere. The stirring was continued for an additional 45 minutes, keeping the temperature at -10° C. A solution of trimethylsilylethoxymethylchloride (2.2 g, 13.2 mmol) in 5 mL THF was added and the mixture stirred overnight at room temperature. The reaction mixture was decomposed with 100 mL distilled water, extracted with ethyl acetate (3×100 mL), and the organic solvent was removed in vacuo. The resulting oily residue was treated with 30 mL IN hydrochloric acid for 1 hour at room temperature after which the reaction mixture was made basic with sodium bicarbonate and extracted with ethyl acetate (3×100 mL). The organic layer was dried over Na2SO4, evaporated to give the crude product which was separated by flash chromatography on silica gel using a mixture of toluene/ethanol 500:30 (v/v) as elution solvent. The fractions, containing the main product (TLC on silica gel, toluene/ethanol 10:2 (v/v), Rf 0.38) were combined and evaporated to dryness in vacuo. Trituration of the oily residue with diethyl ether gave 2.0 g (44%) of α-trimethylsilylethoxymethyl-DL-tryptophan methyl ester, mp 113°-115° C.

Workup

  1. customat -10° C
  2. distillationdistilled water
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. customthe organic solvent was removed in vacuo
  5. additionThe resulting oily residue was treated with 30 mL IN hydrochloric acid for 1 hour at room temperature after which the reaction mixture
  6. extractionextracted with ethyl acetate (3×100 mL)
  7. dry with materialThe organic layer was dried over Na2SO4
  8. customevaporated
  9. customto give the crude product which
  10. customwas separated by flash chromatography on silica gel using
  11. additiona mixture of toluene/ethanol 500:30 (v/v)
  12. washas elution solvent
  13. additionThe fractions, containing the main product (TLC on silica gel, toluene/ethanol 10:2 (v/v), Rf 0.38)
  14. customevaporated to dryness in vacuo

Sources & evidence

ORD record
ord-622546da0a7c4d80bdc50c30b3683c22
Source dataset
uspto-grants-1997_04
Patent number
US05622983

Linked notes

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