Toluene → (R)-4-Isopropyl-3-[(R)-2-methyl-2-(2-trimethylsilanyl-ethoxymethyl)-but-3-enoyl]-oxazolidin-2-one

HRID 2285346Notes

Reaction equation

HRID 2285346 reaction equation
[CH:1]([C@@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[C:10](=[O:15])/[C:11](/[CH3:14])=[CH:12]/[CH3:13])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1(C)C=CC=CC=1.[CH3:33][Si:34]([CH3:41])([CH3:40])[CH2:35][CH2:36][O:37][CH2:38]Cl>>[CH:1]([C@@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[C:10](=[O:15])[C@@:11]([CH3:14])([CH2:38][O:37][CH2:36][CH2:35][Si:34]([CH3:41])([CH3:40])[CH3:33])[CH:12]=[CH2:13])([CH3:3])[CH3:2]

Participants

5

Reactant 4

HCID 1140TolueneHCID 2724254Sodium bis(trimethylsilyl)amideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 86706053(R)-4-Isopropyl-3-((E)-2-methyl-but-2-enoyl)-oxazolidin-2-one

Product 1

HCID 86709642(R)-4-Isopropyl-3-[(R)-2-methyl-2-(2-trimethylsilanyl-ethoxymethyl)-but-3-enoyl]-oxazolidin-2-oneYield 73.2%

Conditions

Temperature
-78 °C

Procedure

Residual moisture in (R)-4-isopropyl-3-((E)-2-methyl-but-2-enoyl)-oxazolidin-2-one (458.9 mg, 2.172 mmol) was removed by azeotroping with anhydrous toluene. A cooled (−78° C.) solution of dried (R)-4-isopropyl-3-((E)-2-methyl-but-2-enoyl)-oxazolidin-2-one in anhydrous toluene (10 mL) was treated dropwise with a solution of sodium bis(trimethylsily)amide in toluene (0.6 M, 5.4 mL, 3.258 mmol). After stirring the yellow solution at −78° C. for 35 min, 2-(trimethylsilyl)ethoxymethyl chloride (1.1 mL, 6.516 mmol) was added. After stirring at 0° C. for 3.5 h, the reaction was quenched with saturated ammonium chloride. The aqueous layer was extracted with dichloromethane (2×). The organics were combined, filtered through a phase separator and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 50 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 9:1 to afford the title compound (543.3 mg, 73%) as a colourless oil and as a 5:1 mixture of diastereoisomers. 1H NMR (300 MHz, CDCl3) δ 0.01 (s, 9H), 0.77-0.99 (m, 8H), 1.49 (s, 3H), 2.36 (d of heptet, J=6.9, 3.8 Hz, 1H), 3.42-3.60 (m, 3H), 4.15-4.31 (m, 3H), 4.49-4.57 (m, 1H), 5.00 (d, J=17.6 Hz, 1H), 5.10 (d, J=10.7, 1H), 6.19 (dd, J=17.8, 10.7 Hz, 1H). LCMS (m/z) 364.1 [M+Na], Tr=3.32 min.

Workup

  1. customby azeotroping with anhydrous toluene
  2. stirringAfter stirring at 0° C. for 3.5 h
  3. customthe reaction was quenched with saturated ammonium chloride
  4. extractionThe aqueous layer was extracted with dichloromethane (2×)
  5. filtrationfiltered through a phase separator
  6. customthe volatiles were removed in vacuo
  7. customThe residue was purified by silica gel chromatography
  8. washeluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 9:1

Sources & evidence

ORD record
ord-4bad8dbb27314015afa25fc97ca5b04f
Source dataset
uspto-grants-2015_09
Patent number
US09145441B2

Reaction notes

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