Hydrochloric Acid → (Tetrahydro-2H-pyran-4-yl)methyl 4-methylbenzenesulfonate

HRID 386853Notes

Reaction equation

HRID 386853 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([CH2:7][OH:8])[CH2:3][CH2:2]1.[OH-].[Na+].[C:11]1([CH3:21])[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1.Cl.CC1CCCCC1>CC1CCCO1>[O:1]1[CH2:6][CH2:5][CH:4]([CH2:7][O:8][S:17]([C:14]2[CH:15]=[CH:16][C:11]([CH3:21])=[CH:12][CH:13]=2)(=[O:19])=[O:18])[CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 73974-Toluenesulfonyl chlorideHCID 7962MethylcyclohexaneHCID 14798Sodium HydroxideHCID 2773573(Oxan-4-yl)methanol

Product 1

HCID 19077576(Tetrahydro-2H-pyran-4-yl)methyl 4-methylbenzenesulfonateYield 99%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent2×

Conditions

Temperature
32.5 °C

Procedure

To a solution of 97 g (810 mmol) of (tetrahydro-pyran-4-yl)-methanol in 2-methyltetrahydrofuran (190 mL) are added 165 mL of 50% aqueous NaOH solution. To this stirred suspension is added dropwise with cooling a solution of p-toluene-sulfonylchloride (283 g, 1.46 mol) in 2-methyltetrahydrofuran (280 mL). The reaction is stirred at 30-35° C. for 18 h. The suspension is poured into a mixture of ice-water (280 mL) and aqueous HCl solution (37%, 203 mL). After addition of methylcyclohexane (1.4 L) and further ice-water (0.2 L), the reaction mixture is stirred for 2 h in an ice-bath. The resulting crystalline precipitate is isolated by filtration and washed with methylcyclohexane (0.5 L) and water (0.5 L). Drying under reduced pressure at 40° C. gave 216 g of toluene-4-sulfonic acid tetrahydro-pyran-4-ylmethyl ester as white crystalline solid. Yield: 99%, ES-MS: m/z 271 [M+H]; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.19-1.35 (2H, m), 1.54-1.63 (2H, m), 1.85-2.02 (1H, m), 2.45 (3H, s), 3.28-3.39 (2H, m), 3.86 (2H, d, J=6.60 Hz), 3.93 (2H, dd, J=11.37, 4.52 Hz), 7.35 (2H, d, J=9.29 Hz), 7.78 (2H, d, J=8.31 Hz)

Workup

  1. additionTo this stirred suspension is added dropwise
  2. stirringthe reaction mixture is stirred for 2 h in an ice-bath
  3. customThe resulting crystalline precipitate is isolated by filtration
  4. washwashed with methylcyclohexane (0.5 L) and water (0.5 L)
  5. customDrying under reduced pressure at 40° C.

Sources & evidence

ORD record
ord-10a31215ef0e4919bba6c9a9859f0344
Source dataset
uspto-grants-2013_02
Patent number
US08372874B2

Reaction notes

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