1-Hydroxybenzotriazole → 2,6-dichloro-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino)carbonyl]benzoic acid, methyl ester

HRID 1726740Notes

Reaction equation

HRID 1726740 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([O-:10])=O)[CH:5]=[C:4]([Cl:11])[C:3]=1[C:12]([O:14][CH3:15])=[O:13].[C:16]1([CH:26]([NH2:28])[CH3:27])[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][CH:17]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[Cl:11][C:4]1[CH:5]=[C:6]([C:8]([NH:28][C@@H:26]([C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)[CH3:27])=[O:10])[CH:7]=[C:2]([Cl:1])[C:3]=1[C:12]([O:14][CH3:15])=[O:13]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 980891-(1-Naphthyl)ethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 857711412,6-Dichlorobenzene-1,4-dicarboxylic acid, 1-methyl ester

Product 1

HCID 865851452,6-dichloro-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino)carbonyl]benzoic acid, methyl esterYield 96%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2,6-dichlorobenzene-1,4-dicarboxylic acid, 1-methyl ester (Example 4; 3.00 g, 12.0 mmol), ®-(+)-1-(1-naphthyl)ethylamine (2.00 g, 11.7 mmol), HBTU (5.68 g, 15.0 mmol), HOBT (2.04 g, 15.1 mmol), and diisopropylethylamine (6.20 g, 48.0 mmol) in N,N-dimethylformamide (50 mL) was stirred at room temperature over the weekend. The solvent was evaporated and ethyl acetate (150 mL) was added. The solution was washed with 1 M HCl (100 mL) and the aqueous layer was back-extracted with ethyl acetate (100 mL). The combined organic layers were washed with saturated aqueous sodium hydrogen carbonate and brine (200 mL each), then dried (MgSO4), filtered, evaporated and chromatographed (30% ethyl acetate/hexanes) to give 2,6-dichloro-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoic acid, methyl ester (4.52 g, 96%) as a white foam.

Workup

  1. customThe solvent was evaporated
  2. additionethyl acetate (150 mL) was added
  3. washThe solution was washed with 1 M HCl (100 mL)
  4. extractionthe aqueous layer was back-extracted with ethyl acetate (100 mL)
  5. washThe combined organic layers were washed with saturated aqueous sodium hydrogen carbonate and brine (200 mL each)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customchromatographed (30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0a69970625754016968922769c67d302
Source dataset
uspto-grants-2009_02
Patent number
US07491741B2

Reaction notes

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