Imidazole → (R)-3-{(R)-2-[(R)-1-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-but-3-enoyl}-4-isopropyl-5,5-dimethyl-oxazolidin-2-one

HRID 2285359Notes

Reaction equation

HRID 2285359 reaction equation
[OH:1][C@@H:2]([C@@H:4]([CH:18]=[CH2:19])[C:5]([N:7]1[C@H:11]([CH:12]([CH3:14])[CH3:13])[C:10]([CH3:16])([CH3:15])[O:9][C:8]1=[O:17])=[O:6])[CH3:3].N1C=CN=C1.[Si:25](Cl)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]>CN(C)C=O>[C:28]([Si:25]([CH3:27])([CH3:26])[O:1][C@@H:2]([C@@H:4]([CH:18]=[CH2:19])[C:5]([N:7]1[C@H:11]([CH:12]([CH3:13])[CH3:14])[C:10]([CH3:16])([CH3:15])[O:9][C:8]1=[O:17])=[O:6])[CH3:3])([CH3:31])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 86709656(R)-3-[(R)-2-((R)-1-hydroxy-ethyl)-but-3-enoyl]-4-isopropyl-5,5-dimethyl-oxazolidin-2-one

Product 1

HCID 86709655(R)-3-{(R)-2-[(R)-1-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-but-3-enoyl}-4-isopropyl-5,5-dimethyl-oxazolidin-2-oneYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A cooled (0° C.) solution of (R)-3-[(R)-2-((R)-1-hydroxy-ethyl)-but-3-enoyl]-4-isopropyl-5,5-dimethyl-oxazolidin-2-one (654 mg, 2.43 mmol, prepared as described in Tetrahedron 2009, 65, 7837-7851) and imidazole (727 mg, 10.68 mmol) in N,N-dimethylformamide (5 mL) was treated with tert-butyldimethylsilyl chloride (474 mg, 3.16 mmol). After stirring for 5 h at room temperature, the reaction was quenched with saturated ammonium chloride. The aqueous layer was extracted with diethyl ether (2×20 mL). The organics were combined and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 25 g Biotage cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 4:1 to afford the title compound (800 mg, 86%) as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 0.03 (s, 3H), 0.09 (s, 3H), 0.84 (s, 9H), 0.92 (d, J=6.7 Hz, 3H), 1.01 (d, J=7.1 Hz, 3H), 1.16 (d, J=6.2 Hz, 3H), 1.40 (s, 3H), 1.50 (s, 3H), 2.05-2.20 (m, 1H), 4.17 (d, J=3.3 Hz, 1H), 4.25-4.40 (m, 1H), 4.67 (t, J=9.1 Hz, 1H), 5.25 (dd, J=10.3, 1.6 Hz, 1H), 5.46 (dd, J=17.2, 1.3 Hz, 1H), 5.65-5.79 (m, 1H).

Workup

  1. customthe reaction was quenched with saturated ammonium chloride
  2. extractionThe aqueous layer was extracted with diethyl ether (2×20 mL)
  3. customthe volatiles were removed in vacuo
  4. customThe residue was purified by silica gel chromatography
  5. washeluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 4:1

Sources & evidence

ORD record
ord-2f4afe0791aa4c4fbe1de2c17eb617d3
Source dataset
uspto-grants-2015_09
Patent number
US09145441B2

Reaction notes

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