1-Hydroxybenzotriazole → 2-Bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoic acid methyl ester

HRID 1058382Notes

Reaction equation

HRID 1058382 reaction equation
C(N(C(C)C)CC)(C)C.[Br:10][C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][C:19]=1[C:20]([O:22][CH3:23])=[O:21])[C:14]([OH:16])=O.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.Cl.[OH:49][C:50]1[CH:51]=[C:52]([CH:55]=[CH:56][CH:57]=1)[CH2:53][NH2:54].ON1C2C=CC=CC=2N=N1>CN(C)C=O>[CH3:23][O:22][C:20](=[O:21])[C:19]1[CH:18]=[CH:17][C:13]([C:14]([NH:54][CH2:53][C:52]2[CH:55]=[CH:56][CH:57]=[C:50]([OH:49])[CH:51]=2)=[O:16])=[CH:12][C:11]=1[Br:10]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 186730263-Bromo-4-(methoxycarbonyl)benzoic acidHCID 220584273-(Aminomethyl)phenol hydrochloride

Product 1

HCID 235607712-Bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoic acid methyl esterYield 73.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Diisopropylethylamine (8.4 mL, 48.2 mmol) was added dropwise to a cooled (˜0° C.) solution of with 3-bromo-4-(methoxycarbonyl)benzoic acid (Example 76; 5.00 g, 19.3 mmol), O-(benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (7.31 g, 19.3 mmol), 3-hydroxybenzylamine hydrochloride salt (Example 69; 3.37 g, 21.2 mmol) and 1-hydroxybenzotriazole (2.6 g, 19.2 mmol) in N,N-dimethylformamide (50 mL). After the solution was allowed to stir at ˜0° C. for 1 h, then at room temperature for 4 h, it was concentrated in vacuo (˜1 mm) to remove most of the N,N-dimethylformamide. The residue was partitioned between ethyl acetate and 1N hydrochloric acid solution (200 mL each). The ethyl acetate layer was washed with 1N hydrochloric acid solution (2×100 mL) and the combined aqueous layers were extracted with ethyl acetate (50 mL). The combined ethyl acetate layers were washed with saturated sodium bicarbonate solution (2×100 mL) and brine, then dried (MgSO4), filtered and evaporated under reduced pressure. The solid residue was crystallized from hot ethyl acetate (˜60 mL) and hexanes (15 mL) to give 2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoic acid methyl ester (5.15 g, 73% yield) as colorless crystals.

Workup

  1. waitat room temperature for 4 h
  2. concentrationit was concentrated in vacuo (˜1 mm)
  3. customto remove most of the N,N-dimethylformamide
  4. customThe residue was partitioned between ethyl acetate and 1N hydrochloric acid solution (200 mL each)
  5. washThe ethyl acetate layer was washed with 1N hydrochloric acid solution (2×100 mL)
  6. extractionthe combined aqueous layers were extracted with ethyl acetate (50 mL)
  7. washThe combined ethyl acetate layers were washed with saturated sodium bicarbonate solution (2×100 mL) and brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customevaporated under reduced pressure
  11. customThe solid residue was crystallized from hot ethyl acetate (˜60 mL) and hexanes (15 mL)

Sources & evidence

ORD record
ord-a4ef44720e5f482da5cb47810ef3967a
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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