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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
ノート
印刷プレビュー

反応式

HRID 1699350 の反応式
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]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 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

生成物 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
収率 64.3%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-dd0bd90d0fe4448caebcc8779a3190d4
出典データセット
uspto-grants-2002_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06346521B1

反応ノート

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