1-Hydroxybenzotriazole → HCID 10815480, compound

HRID 1699354Notes

Reaction equation

HRID 1699354 reaction equation
Cl.C(N=C=NCCCN(C)C)C.[CH3:13][O:14][C:15]1[C:29]([O:30][CH3:31])=[CH:28][C:18]2[CH2:19][C@@H:20]([C:25]([OH:27])=O)[S:21][CH2:22][C:23](=[O:24])[C:17]=2[CH:16]=1.[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:25]([C@@H:20]2[CH2:19][C:18]3[CH:28]=[C:29]([O:30][CH3:31])[C:15]([O:14][CH3:13])=[CH:16][C:17]=3[C:23](=[O:24])[CH2:22][S:21]2)=[O:27])=[CH:47][CH:46]=1)([O:39][CH2:40][CH3:41])=[O:45])[CH3:44]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 88358Diethyl p-aminobenzylphosphonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10588955HCID 10588955, compound

Product 1

HCID 10815480HCID 10815480, compoundYield 40.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.228 g) in dichloromethane (5 ml) was added to a solution of (S)-(+)-1,2,4,5-tetrahydro-7,8-dimethoxy-5-oxo-3-benzothiepin-2-carboxylic acid (0.28 g) and diethyl 4-aminobenzylphosphonate (0.241 g) in N,N-dimethylformamide (DMF) (5 ml) at 0° C., followed by the addition of 1-hydroxybenzotriazole (HOBt) (0.167 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 residue was treated with ethanolisopropyl ether and the solid was removed by filtration. The filtrate was concentrated and the residual oil was subjected to silica gel column chromatography. From the fraction eluted with ethyl acetate-chloroform-methanol (15:15:1, v/v), (2S)-(+)-N-[4-(diethoxyphosphorylmethyl)phenyl]-1,2,4,5-tetrahydro-7,8-dimethoxy-5-oxo-3-benzothiepin-2-carboxamide (0.202 g, 40%) was obtained. Colorless amorphous solid. Melting point 97-99° C. Optical rotation [α]D (23° C.) +155.3° (c=0.50, CHCl3).

Workup

  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. additionthe residue was treated with ethanolisopropyl ether
  6. customthe solid was removed by filtration
  7. concentrationThe filtrate was concentrated
  8. washFrom the fraction eluted with ethyl acetate-chloroform-methanol (15:15:1

Sources & evidence

ORD record
ord-7261c970a3d64b27a46328b310d0a93b
Source dataset
uspto-grants-2002_02
Patent number
US06346521B1

Reaction notes

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