p-Toluenesulfonic acid → 4-(Tetrahydro-pyran-2-yloxy)-but-2-yn-1-ol

HRID 2273837Notes

Reaction equation

HRID 2273837 reaction equation
[O:1]1[CH:6]=[CH:5][CH2:4][CH2:3][C:2]1=[O:7].[CH2:8](O)[C:9]#[C:10][CH2:11][OH:12].CC1C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[K+].[K+]>ClCCl.O>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][C:9]#[C:10][CH2:11][OH:12]

Participants

8

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 80662-Butyne-1,4-diolHCID 11430Potassium CarbonateHCID 1470202H-Pyran-2-one, 3,4-dihydro-HCID 516892Sodium Bicarbonate

Product 1

HCID 111233154-(Tetrahydro-pyran-2-yloxy)-but-2-yn-1-olYield 39%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

3,4-Dihydro-2H-pyron (18.3 mL, 0.196 mol) in dichloromethane (30 mL) was added dropwise over 30 minutes to a stirred solution of 2-butyne-1,4-di-ol (16.832 g, 0.194 mol) and p-TsOH (2.236 g, 11.58 mmol) in DCM (250 mL) at 0° C. After addition, the mixture was stirred at room temperature for 4 hours. Sodium bicarbonate (858 mg) was added. The mixture was stirred for another hour. Water (10 mL) was added, followed by addition of saturated aqueous potassium carbonate (150 mL). The organic phase was separated and washed with brine (200 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure (temperature below 25° C.). The residue was separated by flash column chromatography on silica gel using 5-25% EtOAc/hexane to afford 12.88 g of product (yield: 39%), along with 12.05 g of di-protected side product. 1H-NMR (CDCl3): δ 4.78 (t, J=3.0-3.3 Hz, 1 H), 4.37-4.21 (m, 4 H), 3.86-3.78 (m, 1 H), 3.55-3.50 (m, 1 H), 1.83-1.64 (m, 6 H).

Workup

  1. additionAfter addition
  2. stirringThe mixture was stirred for another hour
  3. customThe organic phase was separated
  4. washwashed with brine (200 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure (temperature below 25° C.)
  7. customThe residue was separated by flash column chromatography on silica gel using 5-25% EtOAc/hexane

Sources & evidence

ORD record
ord-18100d58dbcf4d31a929294a4b0f5cf9
Source dataset
uspto-grants-2015_09
Patent number
US09126926B2

Reaction notes

Loading…