Hydrochloric Acid → 2-Dibenzylamino-3-(4-fluoro-2-nitro-phenoxy)-4-phenyl-butyric acid

HRID 1348624Notes

Reaction equation

HRID 1348624 reaction equation
[CH2:1]([N:8]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH:9]([CH:13]([OH:21])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:10]([OH:12])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].F[C:32]1[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=1[N+:39]([O-:41])=[O:40].Cl>CN(C)C=O>[CH2:22]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH:9]([CH:13]([O:21][C:32]1[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=1[N+:39]([O-:41])=[O:40])[CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C:10]([OH:12])=[O:11])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 677672,5-DifluoronitrobenzeneHCID 670768442-Dibenzylamino-3-hydroxy-4-phenyl-butyric acid

Product 1

HCID 670768382-Dibenzylamino-3-(4-fluoro-2-nitro-phenoxy)-4-phenyl-butyric acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

4.20 g (11.2 mmol) racemic (2R,3R and 2S,3S)-2-dibenzylamino-3-hydroxy-4-phenyl-butyric acid in 14 ml dimethylformamide were added at 0° C. to 1.04 g (23.7 mmol) sodium hydride (55%) in 2.5 ml dimethylformamide. The suspension was stirred for 2 hours and then 2.69 ml (24.6 mmol) 2.5-difluoro-nitrobenzene in 3.5 ml dimethylformamide were added. After stirring overnight at 0° C. the mixture was poured on ice/water. The pH was adjusted to 1 by adding aqueous hydrochloric acid. Extraction with ethylacetate and chromatography on silicagel with dichloromethane/methanol (100:0 to 95:5) yielded 4.02 g (70%) racemic (2R,3R and 2S,3S)-2-dibenzylamino-3-(4-fluoro-2-nitro-phenoxy)-4-phenyl-butyric acid as yellow oil, 1H-NMR (ppm, CDCl3): 2.55–2.63 (m, 1H); 3.54–3.69 (m, 2H); 3.61, 3.66, 3.92, 3.97 (AB, 4H); 4.73–4.80 (m, 1H); 6.14–6.19 (m, 1H); 6.79–6.84 (m,1H); 7.01–7.03 (m, 2H); 7.14–7.16 (m, 3H); 7.2–7.4 (m,11H).

Workup

  1. stirringAfter stirring overnight at 0° C. the mixture
  2. additionwas poured on ice/water
  3. extractionExtraction with ethylacetate and chromatography on silicagel with dichloromethane/methanol (100:0 to 95:5)

Sources & evidence

ORD record
ord-f5a7c4ace65840b29f2adf25b21b9762
Source dataset
uspto-grants-2007_05
Patent number
US07211573B2

Reaction notes

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