Sodium borohydride → Safinamide

HRID 83475Notes

Reaction equation

HRID 83475 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[CH2:5][O:6][C:7]1[CH:19]=[CH:18][C:10]([CH:11]=[N:12][C@@H:13]([CH3:17])[C:14]([NH2:16])=[O:15])=[CH:9][CH:8]=1.[BH4-].[Na+]>CO>[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:11][NH:12][C@@H:13]([CH3:17])[C:14]([NH2:16])=[O:15])=[CH:18][CH:19]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 23659732(S)-(+)-2-[4-(Fluorobenzyloxy-Benzylamino)propionamide]

Product 1

HCID 131682SafinamideYield 89.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
3.5 °C

Procedure

A mixture of (S)-2-[4-(3-fluorobenzyloxy)benzylideneamino]propanamide (III a) (150 g), prepared as described in Example 16a), and methanol (900 mL) is cooled under stirring to 2-5° C. Sodium borohydride (19.0 g) is added in small portions in 2 hours to the previously prepared cold mixture keeping the temperature below 5° C. The mixture is then stirred for additional 20 min at 5° C. The reaction mixture is concentrated under vacuum and worked up as described in Example 2 to give 135 g (89.2% yield) of (5)-2-[4-(3-fluorobenzyloxy)benzylamino]propanamide (Ia) with a HPLC purity of 98.8 (area % determined according to the method of Example 25A and a C,O-dialkylated (S)-2-[3-(3-fluorobenzyl)-4-(3-fluorobenzyloxy)-benzylamino]propanamide content of 0.005% by weight determined by HPLC, according to the method of Example 25B.

Workup

  1. customprepared
  2. temperatureis cooled
  3. customthe temperature below 5° C
  4. stirringThe mixture is then stirred for additional 20 min at 5° C
  5. concentrationThe reaction mixture is concentrated under vacuum

Sources & evidence

ORD record
ord-b123b58e03784966b9fbde488e924024
Source dataset
uspto-grants-2014_09
Patent number
US08846763B2

Reaction notes

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