4-[(3-Fluorophenyl)methoxy]benzaldehyde → Safinamide

HRID 41740Notes

Reaction equation

HRID 41740 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[CH2:5][O:6][C:7]1[CH:14]=[CH:13][C:10]([CH:11]=O)=[CH:9][CH:8]=1.Cl.[NH2:19][C@H:20]([C:22]([NH2:24])=[O:23])[CH3:21].[BH3-]C#N.[Na+]>>[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[CH2:5][O:6][C:7]1[CH:14]=[CH:13][C:10]([CH2:11][NH:19][C@@H:20]([CH3:21])[C:22]([NH2:24])=[O:23])=[CH:9][CH:8]=1.[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[CH2:5][O:6][C:7]1[CH:14]=[CH:13][C:10]([CH:11]=[N:19][C@@H:20]([CH3:21])[C:22]([NH2:24])=[O:23])=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 8801194-[(3-Fluorophenyl)methoxy]benzaldehydeHCID 2775816(S)-2-aminopropanamide hydrochlorideHCID 5003444Sodium cyanoborohydride

Product 2

HCID 131682SafinamideHCID 23659732(S)-(+)-2-[4-(Fluorobenzyloxy-Benzylamino)propionamide]

Procedure

(S)-2-[4-(3-Fluorobenzyloxy)benzylamino]propanamide (Ia) is prepared by reacting 4-(3-fluorobenzyloxy)benzaldehyde (10 mmol), prepared as described in Example 22.1a), and L-alaninamide hydrochloride (1.37 g, 11 mmol) followed by reduction with NaBH3CN (0.50 g, 8 mmol). After working up the reaction mixture and purification by flash-chromatography, (S)-2[4-(3-fluorobenzyloxy)benzalamino]propanamide is isolated as white solid in 68.7% yield. The product has HPLC purity of 96.2 (area %, see Example 25A) and a content of (S)-2-[3-(3-fluorobenzyl)-4-(3-fluorobenzyloxy)-benzylamino]propanamide (IIa) of 0.15% by weight (see Example 25B).

Workup

  1. customprepared
  2. customthe reaction mixture and purification by flash-chromatography

Sources & evidence

ORD record
ord-a68a4e009573423ab0def7757e090f3b
Source dataset
uspto-grants-2013_09
Patent number
US08530701B2

Reaction notes

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