Sodium Methoxide → 2-Methyl-2-[2-(tetrahydro-pyran-4-yl)-ethylsulfanyl]-propionic acid ethyl ester

HRID 1809379Notes

Reaction equation

HRID 1809379 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:3][CH2:2]1.C[O-].[Na+].[CH2:23]([O:25][C:26](=[O:34])[C:27]([S:30]C(=O)C)([CH3:29])[CH3:28])[CH3:24]>C(O)C>[CH2:23]([O:25][C:26](=[O:34])[C:27]([CH3:29])([S:30][CH2:8][CH2:7][CH:4]1[CH2:3][CH2:2][O:1][CH2:6][CH2:5]1)[CH3:28])[CH3:24]

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 57937863Ethyl 2-(acetylthio)-2-methylpropanoateHCID 592679642-(tetrahydro-2H-pyran-4-yl)ethyl 4-methylbenzenesulfonate

Product 1

HCID 592679772-Methyl-2-[2-(tetrahydro-pyran-4-yl)-ethylsulfanyl]-propionic acid ethyl esterYield 108.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 1.9 g (6.7 mmol) of toluene-4-sulfonic acid 2-(tetrahydro-pyran-4-yl)-ethyl ester in ethanol (20 mL) are added 1.4 g (26.8 mmol) of sodium methoxide, followed by 1.27 g (6.7 mmol) of 2-acetylsulfanyl-2-methyl-propionic acid ethyl ester. The reaction mixture is heated in a microwave at 130° C. for 0.5 h. The solvent is removed under reduced pressure. The residue is partitioned between saturated aqueous NaHCO3 solution (25 mL) and DCM (25 mL). The layers are separated and the aqueous phase extracted with DCM (2×25 mL). The combined organic extracts are dried over Na2SO4, filtered and the solvent is removed under reduced pressure to afford 1.9 g of 2-methyl-2-[2-(tetrahydro-pyran-4-yl)-ethylsulfanyl]-propionic acid ethyl ester. Yield: 100%; ES-MS: m/z 261 [M+H]; 1H NMR (250 MHz, CHLOROFORM-d) δ ppm 1.15-1.38 (5H, m), 1.42-1.70 (12H, m), 2.59-2.71 (1H, m), 3.37 (2H, td, J=11.73, 1.98 Hz), 3.95 (2H, ddd, J=11.04, 3.88, 0.91 Hz), 4.18 (2H, q, J=7.16 Hz)

Workup

  1. customThe solvent is removed under reduced pressure
  2. customThe residue is partitioned between saturated aqueous NaHCO3 solution (25 mL) and DCM (25 mL)
  3. customThe layers are separated
  4. extractionthe aqueous phase extracted with DCM (2×25 mL)
  5. dry with materialThe combined organic extracts are dried over Na2SO4
  6. filtrationfiltered
  7. customthe solvent is removed under reduced pressure

Sources & evidence

ORD record
ord-26620676fe8f4287839f6b5e311f290c
Source dataset
uspto-grants-2013_01
Patent number
US08362039B2

Reaction notes

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