1-Hydroxybenzotriazole → N'-[2-(3,4-Difluoro-5-methoxyphenyl)acetyl]-4-benzyloxy-2-ethyl-3-methylbenzohydrazide

HRID 453403Notes

Reaction equation

HRID 453403 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:11][C:12]([OH:14])=O)[CH:5]=[C:6]([O:9][CH3:10])[C:7]=1[F:8].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[CH2:37]([O:44][C:45]1[CH:54]=[CH:53][C:48]([C:49]([NH:51][NH2:52])=[O:50])=[C:47]([CH2:55][CH3:56])[C:46]=1[CH3:57])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>CN(C)C=O.O>[F:1][C:2]1[CH:3]=[C:4]([CH2:11][C:12]([NH:52][NH:51][C:49](=[O:50])[C:48]2[CH:53]=[CH:54][C:45]([O:44][CH2:37][C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)=[C:46]([CH3:57])[C:47]=2[CH2:55][CH3:56])=[O:14])[CH:5]=[C:6]([O:9][CH3:10])[C:7]=1[F:8]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 299208202-(3,4-Difluoro-5-methoxyphenyl)acetic acidHCID 673915534-Benzyloxy-2-ethyl-3-methylbenzohydrazide

Product 1

HCID 67391618N'-[2-(3,4-Difluoro-5-methoxyphenyl)acetyl]-4-benzyloxy-2-ethyl-3-methylbenzohydrazideYield 40.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

340 mg of 2-(3,4-difluoro-5-methoxyphenyl)acetic acid (B2) are dissolved in 7.0 ml of N,N-dimethylformamide under a dry argon atmosphere. 484.3 mg of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, 130.2 mg of N-hydroxybenzotriazole and 526.0 mg of 4-benzyloxy-2-ethyl-3-methylbenzohydrazide (B1) are subsequently added. The reaction solution is stirred at room temperature for 18 h overnight. When the reaction is complete (TLC check), 100 ml of water are added, and the mixture is stirred for 30 min and subsequently extracted three times with 75 ml of ethyl acetate each time. The combined organic phases are dried over Na2SO4, filtered off with suction, and the filtrate obtained is evaporated to dryness in vacuo. The residue is purified by flash column chromatography on silica gel (solvent gradient: dichloromethane/0-20% by vol. of ethanol), giving 321 mg of the title compound as a colourless oil; MS: 937.3 (2M+H+); TLC: Rf=0.50 (dichloromethane/methanol 95:5 parts by volume).

Workup

  1. additionare added
  2. stirringthe mixture is stirred for 30 min
  3. extractionsubsequently extracted three times with 75 ml of ethyl acetate each time
  4. dry with materialThe combined organic phases are dried over Na2SO4
  5. filtrationfiltered off with suction
  6. customthe filtrate obtained
  7. customis evaporated to dryness in vacuo
  8. customThe residue is purified by flash column chromatography on silica gel (solvent gradient: dichloromethane/0-20% by vol. of ethanol)

Sources & evidence

ORD record
ord-d9bd6b471505498791abd92fb26cca0c
Source dataset
uspto-grants-2013_07
Patent number
US08492440B2

Reaction notes

Loading…