Benzylamine → Lacosamide

HRID 2280361노트

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HRID 2280361 반응식
[C:1]([NH:4][C@H:5]([CH2:9][O:10][CH3:11])[C:6]([OH:8])=O)(=[O:3])[CH3:2].ClC(OCC(C)C)=O.CN1CCOCC1.[CH2:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>O1CCCC1>[C:1]([NH:4][C@H:5]([CH2:9][O:10][CH3:11])[C:6]([NH:34][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:8])(=[O:3])[CH3:2]

참가 물질

6

반응물 4

HCID 7504BenzylamineHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 10558933(2R)-2-acetamido-3-methoxypropanoic acid

생성물 1

HCID 219078Lacosamide수율 57%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-10 °C

실험 절차

(R)-2-Acetylamino-3-methoxypropionic acid (8.06 g, 0.05 mol) was dissolved in tetrahydrofuran (80 mL). Isobutyl chloroformate (7.8 mL, 0.06 mol) was added at −10° C. within 10 minutes, followed by 4-methylmorpholine (6.6 mL, 0.06 mol), and the mixture was stirred at −10° C. for 40 minutes. A solution of benzylamine (6.55 mL, 0.06 mol) in tetrahydrofuran (10 mL) was then added at −10° C. The mixture was allowed to warm to room temperature, the solvent evaporated and the residue dissolved in dichloromethane. The solution was successively washed with water (30 mL), 1M HCl (30 mL), 5% sodium hydrogencarbonate solution (30 mL) and again with water (30 mL). The solvent was evaporated and the residue crystallized in ethyl acetate to afford the title compound (7.09 g, 57%). LCMS analysis: 98.0%.

후처리

  1. temperatureto warm to room temperature
  2. customthe solvent evaporated
  3. dissolutionthe residue dissolved in dichloromethane
  4. washThe solution was successively washed with water (30 mL), 1M HCl (30 mL), 5% sodium hydrogencarbonate solution (30 mL) and again with water (30 mL)
  5. customThe solvent was evaporated
  6. customthe residue crystallized in ethyl acetate

출처 및 근거

ORD 기록
ord-a81f8b0b593848c18aba29c6b1b8e73b
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09139513B2

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