Water → (2R)-2-((S)-1-aminomethyl-2,2,2-trifluoro-1-methyl-ethylamino)-2-phenyl-ethanol

HRID 633707Notes

Reaction equation

HRID 633707 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[F:7][C:8]([F:24])([F:23])[C@:9]([NH:13][C@H:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:15][OH:16])([CH3:12])[C:10]#[N:11].O.[OH-].[K+]>O1CCCC1>[NH2:11][CH2:10][C@@:9]([NH:13][C@H:14]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH2:15][OH:16])([CH3:12])[C:8]([F:23])([F:24])[F:7]

Participants

6

Reactant 4

HCID 962Water2×HCID 14797Potassium HydroxideHCID 16081881(2S)-3,3,3-trifluoro-2-((R)-2-hydroxy-1-phenyl-ethylamino)-2-methyl-propionitrileHCID 21226445Aluminium lithium hydride

Product 1

HCID 16083878(2R)-2-((S)-1-aminomethyl-2,2,2-trifluoro-1-methyl-ethylamino)-2-phenyl-ethanolYield 61.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

65.10 mL (65.10 mmol) of a 1 M solution of lithium aluminum hydride in tetrahydrofuran are added to a solution, cooled to 2° C., of 16.80 g (65.10 mmol) of (S)-3,3,3-trifluoro-2-((R)-2-hydroxy-1-phenylethylamino)-2-methylpropionitrile in 50 mL of anhydrous tetrahydrofuran in a three-necked flask under argon. At the end of the addition, the reaction mixture is allowed to warm to room temperature and is then stirred overnight. The mixture obtained is cooled to 0° C., followed by very slow dropwise addition of 12 mL of water. Substantial evolution of gas and a temperature rise to 4° C. are observed. 12 mL of 15% potassium hydroxide and then 25 mL of water are added to the resulting mixture, maintained at 0° C. The white precipitate formed is filtered off and the filtrate obtained is dried over magnesium sulfate and then concentrated under reduced pressure to give 10.50 g of (R)-2-((S)-1-aminomethyl-2,2,2-trifluoro-1-methylethylamino)-2-phenylethanol, the characteristics of which are as follows:

Workup

  1. additionAt the end of the addition
  2. customThe mixture obtained
  3. temperatureis cooled to 0° C.
  4. customto 4° C.
  5. temperaturemaintained at 0° C
  6. customThe white precipitate formed
  7. filtrationis filtered off
  8. customthe filtrate obtained
  9. dry with materialis dried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8d2f70dd1aa445fa94014658dee185f6
Source dataset
uspto-grants-2016_04
Patent number
US09321790B2

Reaction notes

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