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

HRID 1699350
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HRID 1699350 반응식
ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH3:23][C@@H:24]1[S:30][C@@H:29]([C:31]([OH:33])=O)[CH2:28][C:27]2[CH:34]=[C:35]3[O:40][CH2:39][O:38][C:36]3=[CH:37][C:26]=2[C:25]1=[O:41].[NH2:42][C:43]1[CH:55]=[CH:54][C:46]([CH2:47][P:48](=[O:53])([O:51][CH3:52])[O:49][CH3:50])=[CH:45][CH:44]=1>CN(C)C=O.O>[CH3:50][O:49][P:48]([CH2:47][C:46]1[CH:54]=[CH:55][C:43]([NH:42][C:31]([C@H:29]2[CH2:28][C:27]3[CH:34]=[C:35]4[O:40][CH2:39][O:38][C:36]4=[CH:37][C:26]=3[C:25](=[O:41])[C@H:24]([CH3:23])[S:30]2)=[O:33])=[CH:44][CH:45]=1)([O:51][CH3:52])=[O:53]
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참가 물질

7

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 9845635(+/-)-trans-1,2,4,5-Tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acidHCID 12843961Dimethyl [(4-aminophenyl)methyl]phosphonate

생성물 1

HCID 10552598
(2R,4S)-(-)-N-[4-(dimethoxyphosphorylmethyl)phenyl]-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxamide
수율 64.3%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
0 °C

실험 절차

1-Hydroxybenzotriazole (HOBt) (0.51 g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.69 g) were added to a solution of (2R,4S)-(−)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid (0.84 g) and dimethyl 4-aminobenzylphosphonate (0.65 g) in N,N-dimethylformamide (DMF) (10 ml) at 0° C. 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-tetrahydrofuran (3:1). The ethyl acetate layer was washed successively with 1N HCl , water, a saturated sodium hydrogencarbonate solution, water and brine, and dried (MgSO4), after which the solvent was distilled off. The residual solid was collected by filtration, followed by recrystallization from ethanol-hexane to yield (2R,4S)-(−)-N-[4-(dimethoxyphosphorylmethyl)phenyl]-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxamide (0.92 g, 64%). Colorless needles. Melting point 198-199° C. Optical rotation [α]D (23° C.) −198.8° (c=0.50, CHCl3).

후처리

  1. extractionextracted with ethyl acetate-tetrahydrofuran (3:1)
  2. washThe ethyl acetate layer was washed successively with 1N HCl , water
  3. dry with materiala saturated sodium hydrogencarbonate solution, water and brine, and dried (MgSO4)
  4. distillationafter which the solvent was distilled off
  5. filtrationThe residual solid was collected by filtration
  6. customfollowed by recrystallization from ethanol-hexane

출처 및 근거

ORD 기록
ord-dd0bd90d0fe4448caebcc8779a3190d4
출처 데이터셋
uspto-grants-2002_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06346521B1

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