Hydrochloric Acid → 3,3,3-Trifluoro-2-hydroxy-2-methylpropanenitrile
Reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([CH3:5])=[O:4].[C-:8]#[N:9].[C-]#N.[Na+].Cl>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:4])([CH3:5])[C:8]#[N:9]Participants
Procedure
In Scheme 2, 1,1,1-trifluoroacetone (1) is reacted with a cyanide such as sodium cyanide in the presence of an acid such as hydrochloric acid to form racemic 3,3,3-trifluoro-2-hydroxy-2-methylpropanenitrile (2). The racemic 3,3,3-trifluoro-2-hydroxy-2-methylpropanenitrile (2) is then hydrolyzed with, for example, hydrochloric acid or sulfuric acid to provide racemic 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (3). Racemic (3) is then selectively crystallized with a resolving agent such as (lR,2S)-norephedrine (4) to form a salt (5) which may be recrystallized to diastereomeric purity. The purified salt (6) contains (S)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (7). (S)-3,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acid (7) after liberation from the salt is reacted with 4-aminobenzophenone (8) and SOCl2 using an organic base such as triethylamine or Hunig's base to form (S)-(−)-N-(4-benzoylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide (9), which can then be purified by recrystallization.
Sources & evidence
- ORD record
- ord-ef0a6f05644a465c844e764e853b34e9
- Source dataset
- uspto-grants-2001_07
- Patent number
- US06261830B1
Reaction notes
Loading…