Imidazole → Ethyl 5(r)-t-butyldimethylsilyloxyhexanoate

HRID 1037721Notes

Reaction equation

HRID 1037721 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-65c1d404d589410cb87c13c4a5d1c802
Source dataset
uspto-grants-2013_10
Patent number
US08546603B2

Reaction notes

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