Maleic Acid → (+)-(1R,2R)-3-[2-(dimethylamino)methyl-(cyclohex-1-yl)]-phenol maleate

HRID 1363682Notes

Reaction equation

HRID 1363682 reaction equation
[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]\[C:4]([OH:6])=[O:5].[CH3:9][N:10]([CH2:12][C@@H:13]1[CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]1[C:19]1[CH:20]=[C:21]([OH:25])[CH:22]=[CH:23][CH:24]=1)[CH3:11]>C(OCC)(=O)C>[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]\[C:4]([OH:6])=[O:5].[CH3:11][N:10]([CH2:12][C@@H:13]1[CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]1[C:19]1[CH:20]=[C:21]([OH:25])[CH:22]=[CH:23][CH:24]=1)[CH3:9]

Participants

4

Reactant 2

HCID 444266Maleic AcidHCID 9813414Faxeladol

Product 1

HCID 16042847(+)-(1R,2R)-3-[2-(dimethylamino)methyl-(cyclohex-1-yl)]-phenol maleateYield 96.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
70 °C

Procedure

In a glass flask, 1.95 g of (+)-(1R,2R)-3-[2-(dimethylamino)methyl-(cyclohex-1-yl)]-phenol are dissolved at room temperature in 40 ml of ethyl acetate. Then a solution of 0.97 g of maleic acid in 25 ml of ethyl acetate is added dropwise at room temperature. After the addition of approx. half the solution, firstly turbidity forms and then a crystalline precipitate. The suspension is stirred at 70° C. for an hour in a rotary evaporator and then cooled to room temperature. The suspension is then cooled to 4° C. in the refrigerator and the precipitate filtered out. The solid residue is washed once with 4 ml of ethyl acetate and dried by having air drawn through it (5 minutes). 2.815 g (96.4% of theoretical) of (+)-(1R,2R)-3-[2-(dimethylamino)methyl-(cyclohex-1-yl)]-phenol maleate are obtained as crystalline form B (according to the X-ray diffraction pattern) with a melting point of 177-179° C. DSC analysis reveals a peak at 177.7° C.

Workup

  1. additionAfter the addition of approx. half the solution, firstly turbidity forms
  2. temperaturecooled to room temperature
  3. temperatureThe suspension is then cooled to 4° C. in the refrigerator
  4. filtrationthe precipitate filtered out
  5. washThe solid residue is washed once with 4 ml of ethyl acetate
  6. customdried
  7. customdrawn through it (5 minutes)

Sources & evidence

ORD record
ord-5d861f8d3c1b4ac1a4f3911050cc40f2
Source dataset
uspto-grants-2011_02
Patent number
US07884247B2

Reaction notes

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