Propanoic acid, 2-bromo-2-methyl-, ethyl ester → 2-Methyl-2-(tetrahydro-pyran-4-ylmethanesulfonyl)-propionic acid ethyl ester

HRID 553580Notes

Reaction equation

HRID 553580 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([CH2:7]SC(=O)C)[CH2:3][CH2:2]1.[O-]CC.[Na+].Br[C:17]([CH3:24])([CH3:23])[C:18]([O:20][CH2:21][CH3:22])=[O:19].O[O:26][S:27]([O-:29])=O.[K+]>C1(C)C=CC=CC=1.C(O)C.C([N+](CCCC)(CCCC)CCCC)CCC.S([O-])(O)(=O)=O.O.C(O)(=O)C>[CH2:21]([O:20][C:18](=[O:19])[C:17]([CH3:24])([S:27]([CH2:7][CH:4]1[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1)(=[O:29])=[O:26])[CH3:23])[CH3:22]

Participants

10

Reactant 4

HCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 2723922Sodium ethoxideHCID 23707502Potassium hydroxy sulfiteHCID 597040184-(Acetylthiomethyl)tetrahydropyran

Product 1

HCID 597039342-Methyl-2-(tetrahydro-pyran-4-ylmethanesulfonyl)-propionic acid ethyl esterYield 87%

Reagents, catalysts & solvents 5

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Procedure

A solution of 90 g (516 mmol) of thioacetic acid S-(tetrahydro-pyran-4-ylmethyl) ester in toluene (500 mL) under nitrogen atmosphere is cooled in an ice-bath. A solution of sodium ethoxide in ethanol (21%, 231 mL) is added and the reaction stirred for 50 min. Then 76 mL (516 mmol) of ethyl α-bromoisobutyrate are added and the reaction stirred for 1 h. To the reaction mixture are added glacial acetic acid (8.9 mL) and water (500 mL). The organic layer is separated and washed with water (500 mL). A 3-neck round bottom flask is charged with water (500 mL), Oxone® (477 g, 775 mmol) and tetrabutylammonium-hydrogensulfate (5 g, 15 mmol) and the organic layer is added. The biphasic reaction mixture is stirred for 2 d at room temperature. The solids are removed by filtration and the layers of the filtrate are separated. The organic layer is washed with water (2×500 mL). The solvent is removed under reduced pressure and further azeotroped with toluene to give 125 g of 2-methyl-2-(tetrahydro-pyran-4-ylmethanesulfonyl)-propionic acid ethyl ester. Yield: 87%; ES-MS: m/z 279 [M+H]; 1H NMR (250 MHz, CHLOROFORM-d) δ ppm 1.32 (3H, t, J=7.16 Hz), 1.39-1.59 (2H, m), 1.64 (6H, s), 1.81-1.97 (2H, m), 2.29-2.53 (1H, m), 3.15 (2H, d, J=6.55 Hz), 3.45 (2H, dd, J=1.83, 0.30 Hz), 3.88-4.03 (2H, m), 4.26 (2H, d, J=7.16 Hz)

Workup

  1. stirringthe reaction stirred for 1 h
  2. customThe organic layer is separated
  3. washwashed with water (500 mL)
  4. additionthe organic layer is added
  5. customThe biphasic reaction mixture
  6. stirringis stirred for 2 d at room temperature
  7. customThe solids are removed by filtration
  8. customthe layers of the filtrate are separated
  9. washThe organic layer is washed with water (2×500 mL)
  10. customThe solvent is removed under reduced pressure
  11. customfurther azeotroped with toluene

Sources & evidence

ORD record
ord-2c4b584c7d384edb9bdc70d210bfc596
Source dataset
uspto-grants-2011_11
Patent number
US08048899B2

Reaction notes

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