1-Hydroxybenzotriazole → (2S,4R)-(+)-N-[4-(diethoxyphosphorylmethyl)phenyl]-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxamide

HRID 1699355Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1699355
Cl.C(N=C=NCCCN(C)C)C.[CH3:13][C@H:14]1[S:20][C@H:19]([C:21]([OH:23])=O)[CH2:18][C:17]2[CH:24]=[C:25]3[O:30][CH2:29][O:28][C:26]3=[CH:27][C:16]=2[C:15]1=[O:31].[NH2:32][C:33]1[CH:47]=[CH:46][C:36]([CH2:37][P:38](=[O:45])([O:42][CH2:43][CH3:44])[O:39][CH2:40][CH3:41])=[CH:35][CH:34]=1.ON1C2C=CC=CC=2N=N1>ClCCl.CN(C)C=O.O>[CH2:43]([O:42][P:38]([CH2:37][C:36]1[CH:35]=[CH:34][C:33]([NH:32][C:21]([C@@H:19]2[CH2:18][C:17]3[CH:24]=[C:25]4[O:30][CH2:29][O:28][C:26]4=[CH:27][C:16]=3[C:15](=[O:31])[C@@H:14]([CH3:13])[S:20]2)=[O:23])=[CH:47][CH:46]=1)([O:39][CH2:40][CH3:41])=[O:45])[CH3:44]

Komponenten

8

Edukt 4

HCID 757711-HydroxybenzotriazoleHCID 88358Diethyl p-aminobenzylphosphonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10802686(2S,4R)-(+)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid

Produkt 1

HCID 10649211(2S,4R)-(+)-N-[4-(diethoxyphosphorylmethyl)phenyl]-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxamideAusbeute 41 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.69 g) in dichloromethane (12 ml) was added to a solution of (2S,4R)-(+)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid (0.84 g) and diethyl 4-aminobenzylphosphonate (0.73 g) in N,N-dimethylformamide (DMF) (12 ml) at 0° C., followed by the addition of 1-hydroxybenzotriazole (HOBt) (0.51 g). This mixture was stirred at 0° C. for 1 hour and at room temperature for 15 hours, after which it was poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried (MgSO4), after which the solvent was distilled off; the residual crystals were collected by filtration, followed by recrystallization from ethyl acetate-hexane and successively from methanol-hexane to yield (2S,4R)-(+)-N-[4-(diethoxyphosphorylmethyl)phenyl]-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxamide (0.62 g, 41%). Colorless prisms. Melting point 183-184° C. Optical rotation [α](23° C.) +190.5° (c=0.50, CHCl3).

Aufarbeitung

  1. extractionextracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with water
  3. dry with materialdried (MgSO4)
  4. distillationafter which the solvent was distilled off
  5. filtrationthe residual crystals were collected by filtration
  6. customfollowed by recrystallization from ethyl acetate-hexane and successively from methanol-hexane

Quellen und Nachweise

ORD-Eintrag
ord-b506097fa20d44b68964ea135452a7fe
Quelldatensatz
uspto-grants-2002_02
Patentnummer
US06346521B1

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