Acetic Anhydride → Lacosamide

HRID 1852053Notes

Reaction equation

HRID 1852053 reaction equation
[NH2:1][C@H:2]([CH2:13][O:14][CH3:15])[C:3]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].C(N(CC)CC)C.[C:23](OCC)(=[O:25])[CH3:24].C(OC(=O)C)(=O)C>C1CCCCC1>[C:23]([NH:1][C@H:2]([CH2:13][O:14][CH3:15])[C:3]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4])(=[O:25])[CH3:24]

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 10104501(R)-2-Amino-N-benzyl-3-methoxypropionamide

Product 1

HCID 219078Lacosamide

Reagents, catalysts & solvents 1

HCID 8078CyclohexaneSolvent

Conditions

Temperature
27.5 °C

Procedure

To a solution of (2R)-2-Amino-N-benzyl-3-methoxypropanamide (60.0 gms) and triethylamine (7.29 gms) in cyclohexane (600 ml) charged ethyl acetate (540 ml) and added acetic anhydride (35.29 gms) slowly maintaining the temperature at 25-30° C. in 15-20 minutes. Raised the temperature of the reaction mass to 35-40° C. and maintained for 4 hours. After completion of the reaction the reaction mass was cooled to 0 to 5° C. within 1 hour and maintained for 1.5 hours. Filtered the reaction mass at 0-5° C. and washed with cooled 1:1 mixture of ethyl acetate: cyclohexane (2×120 ml). The wet solid was taken in diethyl ether (612 ml) and stirred for 6 hours at 20-25° C. Filtered the product (2R)-2-acetamido-N-benzyl-3-methoxypropanamide and washed with diethyl ether and dried at 50-55° C. till constant weight.

Workup

  1. temperatureRaised the temperature of the reaction mass to 35-40° C.
  2. temperaturemaintained for 4 hours
  3. customAfter completion of the reaction the reaction mass
  4. temperaturewas cooled to 0 to 5° C. within 1 hour
  5. temperaturemaintained for 1.5 hours
  6. filtrationFiltered the reaction mass at 0-5° C.
  7. washwashed
  8. temperaturewith cooled
  9. addition1:1 mixture of ethyl acetate
  10. filtrationFiltered the product (2R)-2-acetamido-N-benzyl-3-methoxypropanamide
  11. washwashed with diethyl ether
  12. customdried at 50-55° C. till constant weight

Sources & evidence

ORD record
ord-a3d21c429c944ae3a4b0c23487ad5361
Source dataset
uspto-grants-2015_02
Patent number
US08957252B2

Reaction notes

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