Imidazole → Ethyl 4-(tert-butyldimethylsilyloxy)-2-ethylcyclopentanecarboxylate

HRID 1969640Notes

Reaction equation

HRID 1969640 reaction equation
[C:1]([O:9][CH:10]1CC(C2N3C4C=CN(S(C5C=CC(C)=CC=5)(=O)=O)C=4N=CC3=NN=2)C(CC)[CH2:11]1)(=[O:8])C1C=CC=CC=1.[CH3:39][C:40]([Si:43](Cl)([CH3:45])[CH3:44])([CH3:42])[CH3:41].N1C=CN=C1.[CH3:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58].CN(C=[O:63])C>>[Si:43]([O:63][CH:54]1[CH2:53][CH:52]([C:1]([O:9][CH2:10][CH3:11])=[O:8])[CH:56]([CH2:57][CH3:58])[CH2:55]1)([C:40]([CH3:42])([CH3:41])[CH3:39])([CH3:45])[CH3:44]

Participants

6

Reactant 5

HCID 795ImidazoleHCID 6228DimethylformamideHCID 8900HeptaneHCID 28928tert-Butyldimethylsilyl chlorideHCID 585576193-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl benzoate

Product 1

HCID 58557197Ethyl 4-(tert-butyldimethylsilyloxy)-2-ethylcyclopentanecarboxylateYield 64%

Procedure

To a solution of ethyl 2-ethyl-4-hydroxycyclopentanecarboxylate (4.97 g, 26.7 mmol, prepared using II from Preparation #P.1, SS with NaOH)) in DMF (9 mL) was added TBDMS-Cl (4.83 g, 32.1 mmol) and imidazole (4.55 g, 66.8 mmol). The reaction mixture was stirred at ambient temperature for about 3 h. Heptane (30 mL) was added. The layers were separated and the bottom layer (DMF layer) was extracted with heptane (3×30 mL). The combined organic extracts were washed with water (2×30 mL), brine (30 mL), dried over anhydrous MgSO4, filtered and concd under reduced pressure. The material was purified by silica gel chromatography eluting with a gradient of 0-15% EtOAc in heptane to afford ethyl 4-(tert-butyldimethylsilyloxy)-2-ethylcyclopentanecarboxylate (5.16 g, 64%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 4.45 (m, 1H), 4.11 (m, 2H), 3.08 (m, 1H), 2.34 (m, 1H), 2.18 (m, 1H), 1.75 (m, 2H), 1.57 (m, 1H), 1.41 (m, 1H), 1.25 (m, 3H), 1.10 (m, 1H), 0.90 (m, 3H), 0.87 (s, 9H), 0.03 (s, 6H).

Workup

  1. customThe layers were separated
  2. extractionthe bottom layer (DMF layer) was extracted with heptane (3×30 mL)
  3. washThe combined organic extracts were washed with water (2×30 mL), brine (30 mL)
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. customThe material was purified by silica gel chromatography
  7. washeluting with a gradient of 0-15% EtOAc in heptane

Sources & evidence

ORD record
ord-565c4cfe6a904207a983cda24e609d51
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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