2,3-Dimethylphenol → HCID 68894799, compound

HRID 1784795Notes

Reaction equation

HRID 1784795 reaction equation
[CH:1]12[O:7][CH:6]1[CH2:5][CH2:4][N:3]([C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9])[CH2:2]2.[CH3:18][C:19]1[C:24]([CH3:25])=[CH:23][CH:22]=[CH:21][C:20]=1[OH:26].[OH-].[Na+]>C(#N)C.O.[Cl-].[Na+].O>[CH2:11]([O:10][C:8]([N:3]1[CH2:4][CH2:5][C@@H:6]([O:26][C:20]2[CH:21]=[CH:22][CH:23]=[C:24]([CH3:25])[C:19]=2[CH3:18])[C@H:1]([OH:7])[CH2:2]1)=[O:9])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 3

HCID 106872,3-DimethylphenolHCID 14798Sodium Hydroxide2×HCID 13186888Benzyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate

Product 1

HCID 68894799HCID 68894799, compoundYield 51.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Benzyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (21.0 g, 92.0 mmol) was added to a stirred solution of 2,3-dimethylphenol (23.0 g, 188 mmol) and aqueous sodium hydroxide (100 ml, 2N, 200 mmol) in acetonitrile (400 ml). The reaction mixture was heated at reflux for 14 h. On cooling to room temperature, the reaction mixture was concentrated in vacuo before dilution with water (500 ml). Extraction with dichloromethane (4×100 ml) was followed by washing of the combined organics with aqueous sodium hydroxide (100 ml, 3N, 300 mmol), water (100 ml) and brine (100 ml). The organics were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to furnish a crude product. Purification was carried out by silica gel chromatography using a gradient eluent system of iso-hexanes and ethyl acetate (100% iso-hexanes to 80:20 iso-hexanes:ethyl acetate) to furnish trans-benzyl-4-(2,3-dimethylphenoxy)-3-hydroxypiperidine-1-carboxylate as a pale yellow syrup (16.8 g, 50%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 14 h
  3. concentrationthe reaction mixture was concentrated in vacuo before dilution with water (500 ml)
  4. extractionExtraction with dichloromethane (4×100 ml)
  5. dry with materialThe organics were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto furnish a crude product
  9. customPurification

Sources & evidence

ORD record
ord-7baff472628c4fd88598f675370fa9fd
Source dataset
uspto-grants-2009_03
Patent number
US07504419B2

Reaction notes

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