Water → HCID 59769753, compound

HRID 2220357Notes

Reaction equation

HRID 2220357 reaction equation
[OH-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([OH:11])[CH:7]=[C:8]([Cl:10])[CH:9]=1.[CH2:12]([C@H:15]1[O:17][C@@H:16]1[CH2:18][OH:19])[CH2:13][CH3:14].O>C1COCC1.[Cl-].[Na+].O.ClCCl>[Cl:3][C:4]1[CH:5]=[C:6]([CH:7]=[C:8]([Cl:10])[CH:9]=1)[O:11][C@@H:15]([CH2:12][CH2:13][CH3:14])[C@H:16]([OH:17])[CH2:18][OH:19]

Participants

8

Reactant 4

HCID 962WaterHCID 115713,5-DichlorophenolHCID 14798Sodium HydroxideHCID 11073386(2R,3R)-(+)-3-PROPYLOXIRANEMETHANOL, 97% (94% EE/GLC)

Product 1

HCID 59769753HCID 59769753, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
75 °C

Procedure

Add sodium hydroxide (1N, 9 mL) to a stirred solution of 3,5-dichlorophenol in THF (9 mL) followed by a solution of (R,R)-(3-propyl-oxiranyl)-methanol in THF (5 mL). Heat the reaction mixture at 75° C. overnight, cool to room temperature, add water, brine and dichloromethane, and separate the layers. The aqueous layer is extracted with dichloromethane, the combined organic extracts are washed successively with 1N sodium hydroxide and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Analysis of the crude reaction mixture by 1H NMR reveals a ˜2:1 mixture of the C-3:C-1 adducts. Purification of the crude residue on silica gel eluting with 0-25% EtOAc/hexanes gives the major title compound (332 mg, 26%). 1H NMR (DMSO-d6): 0.86 (dd, 3H, J=4, 4 Hz), 1.21-1.48 (m, 2H), 1.52-1.72 (m, 2H), 3.28-3.45 (m, 2H), 3.60-3.67 (m, 2H), 4.37-4.44 (m, 1H), 4.69 (dd, 1H, J=6, 6 Hz), 4.88 (d, 1H, J=5 Hz), 7.01-7.10 (m, 3H).

Workup

  1. temperaturecool to room temperature
  2. customseparate the layers
  3. extractionThe aqueous layer is extracted with dichloromethane
  4. washthe combined organic extracts are washed successively with 1N sodium hydroxide and water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customAnalysis of the crude reaction mixture by 1H NMR
  8. additiona ˜2:1 mixture of the C-3
  9. customPurification of the crude residue on silica gel eluting with 0-25% EtOAc/hexanes

Sources & evidence

ORD record
ord-f5c6ff974c5041ab892c980c12cc4f98
Source dataset
uspto-grants-2008_08
Patent number
US07417064B2

Reaction notes

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