Methyl iodide → (3R,5S)-5-[(1S)-1-[tert-butyl(diphenyl)silyl]oxypropyl]-3-methyl-tetrahydrofuran-2-one

HRID 60741Notes

Reaction equation

HRID 60741 reaction equation
[Si:1]([O:18][C@H:19]([C@H:22]1[O:26][C:25](=[O:27])[CH2:24][CH2:23]1)[CH2:20][CH3:21])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:28]([N-]C(C)C)(C)C.[Li+].IC>C1COCC1>[Si:1]([O:18][C@H:19]([C@H:22]1[O:26][C:25](=[O:27])[C@H:24]([CH3:28])[CH2:23]1)[CH2:20][CH3:21])([C:14]([CH3:15])([CH3:16])[CH3:17])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 131737106HCID 131737106, compound2×

Product 1

HCID 131737105(3R,5S)-5-[(1S)-1-[tert-butyl(diphenyl)silyl]oxypropyl]-3-methyl-tetrahydrofuran-2-oneYield 87.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (5S)-5-[(1S)-1-[tert-butyl(diphenyl)silyl]oxypropyl]tetrahydrofuran-2-one (Compound 28e-S, 3.0 g, 7.8 mmol) in THF (60 mL) at −78° C. was added lithium diisopropylamide (2M in THF, 5.9 mL, 11.8 mmol) dropwise. After addition, the reaction was stirred at −78° C. for 1 hour. To the mixture was added iodomethane (5.5 g, 39 mmol) and the mixture was stirred at −78° C. for another 1 hour. The mixture was quenched with saturated NH4Cl solution (40 mL), extracted with EtOAc (100 mL) twice. The organic layers were combined, washed with brine (50 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 1:20 to 1:10 EtOAc in petroleum ether) to afford 2.7 g of (3R,5S)-5-[(1S)-1-[tert-butyl(diphenyl)silyl]oxypropyl]-3-methyl-tetrahydrofuran-2-one (compound 28f) as a colourless oil. (Refer to Tetrahedron. 1997, 53, 6281-6294).

Workup

  1. additionAfter addition
  2. stirringthe mixture was stirred at −78° C. for another 1 hour
  3. customThe mixture was quenched with saturated NH4Cl solution (40 mL)
  4. extractionextracted with EtOAc (100 mL) twice
  5. washwashed with brine (50 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography on silica gel (eluting with 1:20 to 1:10 EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-a4559d142634422a9d13d87a1538b803
Source dataset
uspto-grants-2016_09
Patent number
US09441008B2

Reaction notes

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