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Trifluoroacetic acid → 4-acetyl-N-(3-methoxybenzyl)benzamide

HRID 31739
Notes
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Reaction equation

HRID 31739 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH2:6][NH2:7].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:44]([C:47]1[CH:55]=[CH:54][C:50]([C:51](O)=[O:52])=[CH:49][CH:48]=1)(=[O:46])[CH3:45].CN1CCOCC1.C(O)(C(F)(F)F)=O>CN1C(=O)CCC1.ClCCl>[C:44]([C:47]1[CH:55]=[CH:54][C:50]([C:51]([NH:7][CH2:6][C:5]2[CH:8]=[CH:9][CH:10]=[C:3]([O:2][CH3:1])[CH:4]=2)=[O:52])=[CH:49][CH:48]=1)(=[O:46])[CH3:45]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 114704-Acetylbenzoic AcidHCID 211563-MethoxybenzylamineHCID 2724699PyBOP

Product 1

HCID 598408954-acetyl-N-(3-methoxybenzyl)benzamideYield 97%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

The Sasrin resin was prepared as described in Step 2 of Example 3. The resin (500 mg) was heated with a solution of 3-methoxybenzylamine (600 μl ) in NMP (6 ml) at 70° C. for 4 hours. The resin was then washed with DMF and dichloromethane and then shaken with a solution of PyBop® (1.04 g, 2 mmol), 4-acetylbenzoic acid (0.33 g, 2 mmol), 4-methylmorpholine (4 mmol) in NMP (6 ml) at room temperature overnight. A small aliquot of the resin was treated with 20% TFA in dichloromethane to give the intermediate, (4-acetylphenyl)-N-[(3-methoxyphenyl)methyl]carboxamide (HPLC: 23.94 min (97%); MS; MH+=284 (as required)). The resin was then heated at 95° C. for 7 hours in DMFDMA (5 ml).

Workup

  1. customThe Sasrin resin was prepared
  2. washThe resin was then washed with DMF and dichloromethane

Sources & evidence

ORD record
ord-1818aeeacb4c4b8996cc79a60014620c
Source dataset
uspto-grants-2008_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07425557B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes