Water → (R)-3,4,4-Trimethoxytetrahydro-2H-pyran

HRID 1747112Notes

Reaction equation

HRID 1747112 reaction equation
[CH3:1][O:2][C:3]1([O:10][CH3:11])[CH2:8][CH2:7][O:6][CH2:5][C@H:4]1[OH:9].[CH3:12]C([O-])(C)C.[K+].S(OC)(OC)(=O)=O.O>C1COCC1.C(Cl)Cl>[CH3:12][O:9][C@H:4]1[C:3]([O:10][CH3:11])([O:2][CH3:1])[CH2:8][CH2:7][O:6][CH2:5]1

Participants

7

Reactant 4

HCID 962WaterHCID 6497Dimethyl SulfateHCID 116654592H-PYRAN-3-OL, TETRAHYDRO-4,4-DIMETHOXY-, (3R)-HCID 23665647Potassium tert-butoxide

Product 1

HCID 86708124(R)-3,4,4-Trimethoxytetrahydro-2H-pyranYield 99%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A 12-L 4-neck round bottom flask equipped with a overhead air stirrer, addition funnel with nitrogen inlet adapter, condenser, and thermocouple was charged with (R)-4,4-dimethoxytetrahydro-2H-pyran-3-ol (as prepared in the previous step, 163 g, 1.0 mol) in THF (2.4 L) and stirred in ice/acetone bath until <0° C. KOtBu (113 g, 1.0 mol) was added in one portion, and after stirring 45 min, dimethyl sulfate (95 mL, 1.0 mol) was added via addition funnel over 15 min. The reaction was allowed to stir at room temperature for 2 h. The reaction mixture was poured into a reparatory flask containing H2O (1.2 L) and CH2Cl2 (1.2 L) and the layers were separated. The aqueous layer was back-extracted with CH2Cl2 (900 mL). The combined organic layers were washed with brine (1.0 L; Note: organic layer was on top), dried over MgSO4, filtered and evaporated to afford the title compound (177.1 g, 99%, chiral GC 94.4% ee) as a light yellow oil.

Workup

  1. customA 12-L 4-neck round bottom flask equipped with a overhead air stirrer, addition funnel with nitrogen inlet adapter, condenser
  2. stirringto stir at room temperature for 2 h
  3. additionThe reaction mixture was poured into a reparatory flask
  4. customthe layers were separated
  5. extractionThe aqueous layer was back-extracted with CH2Cl2 (900 mL)
  6. washThe combined organic layers were washed with brine (1.0 L; Note: organic layer was on top)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-0b318d7dfbbe4e9fa076d42ac3221504
Source dataset
uspto-grants-2015_10
Patent number
US09150532B2

Reaction notes

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