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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
Notes
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Reaction equation

HRID 1699350 reaction equation
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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 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

Product 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
Yield 64.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-dd0bd90d0fe4448caebcc8779a3190d4
Source dataset
uspto-grants-2002_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06346521B1

Reaction notes

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