Imidazole → Ethyl 5(r)-t-butyldimethylsilyloxyhexanoate

HRID 1694324Notes

Reaction equation

HRID 1694324 reaction equation
[OH:1][C@H:2]([CH3:11])[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].N1C=CN=C1.[Si:17](Cl)([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]>CN(C=O)C>[Si:17]([O:1][C@H:2]([CH3:11])[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 11073717Ethyl 5(R)-hydroxyhexanoate

Product 1

HCID 10516491Ethyl 5(r)-t-butyldimethylsilyloxyhexanoateYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of ethyl 5(R)-hydroxyhexanoate 3 (1.80 g, 11.24 mmol), imidazole (2.3 g, 33.8 mmol), and t-butyldimethylsilyl chloride (2.54 g, 16.85 mmol) in 30 mL of DMF was stirred at 23° C. overnight (19 h). The solvent (DMF) was then removed in vacuo and aqueous saturated sodium bicarbonate (100 mL) was added followed by ethyl acetate (100 mL). The layers were separated and the aqueous layer was re-extracted with 100 mL of EtOAc. The combined organic layers were washed with water, brine, and dried over anhydrous sodium sulfate. Flash column chromatographic purification on 30 g of silica gel yielded 2.71 g (88%) of TBDMS-ether 4 (G.C. purity of 99+A %); 1H NMR (CDCl3): 0.04 (s, 6H), 0.91 (s, 9H), 1.18 (d, J=6 Hz, 3H), 1.25 (t, J=7.2 Hz, 3H), 1.42 (m, 2H), 1.65 (m, 2H), 2.39 (t, J=7.5 Hz, 2H), 3.79 (m, J=6 Hz, 1H), 4.12 (q, J=7.2 Hz, 2H).

Workup

  1. customThe solvent (DMF) was then removed in vacuo and aqueous saturated sodium bicarbonate (100 mL)
  2. additionwas added
  3. customThe layers were separated
  4. extractionthe aqueous layer was re-extracted with 100 mL of EtOAc
  5. washThe combined organic layers were washed with water, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customFlash column chromatographic purification on 30 g of silica gel

Sources & evidence

ORD record
ord-2acd8b13dfb64c339b9debb45f54ee42
Source dataset
uspto-grants-2012_04
Patent number
US08158676B2

Reaction notes

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