Sodium Hydroxide → 4-[[(E)-(1-benzylindol-2-yl)methylideneamino]oxymethyl]-2-bromobenzoic acid

HRID 1392274Notes

Reaction equation

HRID 1392274 reaction equation
C[O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][O:11][NH2:12])=[CH:6][C:5]=1[Br:13].[CH2:15]([N:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=[C:23]1[CH:31]=O)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[OH-].[Na+]>>[CH2:15]([N:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=[C:23]1/[CH:31]=[N:12]/[O:11][CH2:10][C:7]1[CH:8]=[CH:9][C:4]([C:3]([OH:2])=[O:14])=[C:5]([Br:13])[CH:6]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

4

Reactant 3

HCID 14798Sodium HydroxideHCID 129167171-benzyl-1H-indole-2-carbaldehydeHCID 691941704-Aminooxymethyl-2-bromo-benzoic acid methyl ester

Product 1

HCID 116340414-[[(E)-(1-benzylindol-2-yl)methylideneamino]oxymethyl]-2-bromobenzoic acidYield 51%

Procedure

To a solution of 4-aminooxymethyl-2-bromo-benzoic acid methyl ester (0.21 g, 0.81 mmol) and 1-benzyl-1H-indole-2-carbaldehyde (0.19 g, 0.81 mmol) in 10/5/3 tetrahydrofuran/ethanol/water (18 mL) was added 2.5 M sodium hydroxide solution (3 mL). This mixture was heated to reflux for 3 hours and then allowed to cool back to room temperature. The mixture was concentrated to approximately 1/4 volume and partitioned between ethyl acetate and water. The aqueous layer was acidified to approximately pH 1 using 1 N hydrochloric acid. The layers were then separated. The aqueous layer was extracted with one additional portion of ethyl acetate. The organics were combined, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography through silica gel using ethyl acetate/hexanes (20/80 with 1% formic acid) to give 4-[({[(1E)-(1-benzyl-1H-indol-2-yl)methylidene]amino }oxy)methyl]-2-bromobenzoic acid (0.19 g, 51%) as an off-white powder. mp=148-149° C. 1H NMR (400 MHz, DMSO-d6); δ 13.35 (bs, 1H), 8.51 (s, 1H), 7.66 (m, 2H), 7.60 (d, 1H), 7.48 (d, 1H), 7.34 (d, 1H), 7.21-7.15 (m,4H), 7.06 (t, 1H), 6.93 (s, 1H), 6.90 (d, 2H), 5.70 (s, 2H), 5.14 (s, 2H). Mass spec; (ES+) m/z 462.9, (ES−) m/z 461.3. Elemental analysis; Calculated for C24H19BrN2O3: C, 62.22; H, 4.13; N, 6.05. Found: C, 62.07; H, 4.38; N, 5.88.

Workup

  1. temperatureThis mixture was heated
  2. temperatureto reflux for 3 hours
  3. concentrationThe mixture was concentrated to approximately 1/4 volume
  4. custompartitioned between ethyl acetate and water
  5. customThe layers were then separated
  6. extractionThe aqueous layer was extracted with one additional portion of ethyl acetate
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude material was purified by flash chromatography through silica gel

Sources & evidence

ORD record
ord-f1b801c2940b4d3d9e9a209eada20978
Source dataset
uspto-grants-2008_03
Patent number
US07342039B2

Reaction notes

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