Sodium borohydride → Priralfinamide

HRID 41733Notes

Reaction equation

HRID 41733 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[CH2:4][O:5][C:6]1[CH:18]=[CH:17][C:9]([CH:10]=[N:11][C@@H:12]([CH3:16])[C:13]([NH2:15])=[O:14])=[CH:8][CH:7]=1.[BH4-].[Na+]>CO>[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:10][NH:11][C@@H:12]([CH3:16])[C:13]([NH2:15])=[O:14])=[CH:17][CH:18]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 23659931(S)-2-[4-(2-fluorobenzyloxy)benzylideneamino]propanamide

Product 1

HCID 5745207PriralfinamideYield 95%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
3.5 °C

Procedure

A mixture of (S)-2-[4-(2-fluorobenzyloxy)benzylideneamino]propanamide (IIIb) prepared as described above (30 g) and methanol (180 mL) is cooled under stirring to 2-5° C. Sodium borohydride (3.8 g) is added in eighteen small portions in 90 min to the previously prepared cold mixture keeping the temperature below 5° C. The mixture is then stirred for additional 10 min at 5° C. The reaction mixture is concentrated under vacuum and worked up as described in Example 2 to provide 28.75 g (95% yield) of (S)-2-[4-(2-fluorobenzyloxy)benzylamino]propanamide (ralfinamide, Ib) with a HPLC purity of 99.5 (area %) determined according to the method of Example 25A and a C,O-dialkylated (S)-2-[3-(2-fluorobenzyl)-4-(2-fluorobenzyloxy)-benzylamino]propanamide content less than 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 10 min at 5° C
  5. concentrationThe reaction mixture is concentrated under vacuum

Sources & evidence

ORD record
ord-6506d31e79be496dafcdb4ce8c7e181a
Source dataset
uspto-grants-2013_09
Patent number
US08530701B2

Reaction notes

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