Sodium Hydroxide → 4-[3-[(E)-(1-benzylindol-3-yl)methylideneamino]oxypropoxy]-3-[4-(trifluoromethyl)phenyl]benzoic acid

HRID 1392283Notes

Reaction equation

HRID 1392283 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)[C:8]([O:11][CH2:12][CH2:13][CH2:14]Br)=[CH:9][CH:10]=1)=[O:4].[CH2:26]([N:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:35]([CH:42]=[N:43][OH:44])=[CH:34]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[OH-].[Na+]>>[CH2:26]([N:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:35](/[CH:42]=[N:43]/[O:44][CH2:14][CH2:13][CH2:12][O:11][C:8]2[C:7]([C:16]3[CH:17]=[CH:18][C:19]([C:22]([F:24])([F:23])[F:25])=[CH:20][CH:21]=3)=[CH:6][C:5]([C:3]([OH:2])=[O:4])=[CH:10][CH:9]=2)=[CH:34]1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

4

Reactant 3

HCID 14798Sodium HydroxideHCID 46376791-Benzyl-1H-indole-3-carbaldehyde oximeHCID 691956816-(3-Bromo-propoxy)-4'-trifluoromethyl-biphenyl-3-carboxylic acid methyl ester

Product 1

HCID 114672564-[3-[(E)-(1-benzylindol-3-yl)methylideneamino]oxypropoxy]-3-[4-(trifluoromethyl)phenyl]benzoic acidYield 10%

Procedure

To a solution of 6-(3-bromo-propoxy)-4′-trifluoromethyl-biphenyl-3-carboxylic acid methyl ester (0.30 g, 0.72 mmol) and 1-benzyl-1H-indole-3-carbaldehyde oxime (0.18 g, 0.72 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 2.5 hours and then allowed to cool back to room temperature. The mixture was 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 6-[3-({[(1E)-(1-benzyl-1H-indol-3-yl)methylidene]amino }oxy)propoxy]-4′-(trifluoromethyl)-1,1′-biphenyl-3-carboxylic acid (0.041 g, 10%) as a white solid. mp=193-194° C. 1H NMR (400 MHz, DMSO-d6); δ 8.24 (s, 1H), 7.94 (d, 1H), 7.90-7.86 (m, 3H), 7.78-7.74 (m, 5H), 7.40 (d, 1H), 7.25-7.11 (m, 7H), 5.43 (s, 2H), 4.26 (t, 2H), 4.23 (t, 2H), 2.49 (m, 2H). Mass spec; (ES+) m/z 5.73.1 (ES−) m/z 571.5. Elemental analysis; Calculated for C33H27F3N2O4: C, 69.22; H, 4.75; N, 4.89. Found: C, 68.62; H, 4.93; N, 4.81.

Workup

  1. temperatureThis mixture was heated
  2. temperatureto reflux for 2.5 hours
  3. customThe mixture was partitioned between ethyl acetate and water
  4. customThe layers were then separated
  5. extractionThe aqueous layer was extracted with one additional portion of ethyl acetate
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by flash chromatography through silica gel

Sources & evidence

ORD record
ord-7c8953404ac8407fb2eb3d4875825a8b
Source dataset
uspto-grants-2008_03
Patent number
US07342039B2

Reaction notes

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