Aluminium lithium hydride → (R)-4-[2-(1-Methyl-2,2,2-trifluoroethylamino)-thiazol-4-yl]-benzylamine

HRID 1191081Notes

Reaction equation

HRID 1191081 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][C@@H:8]([NH:13][C:14]1[S:15][CH:16]=[C:17]([C:19]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=2)[N:18]=1)[C:9]([F:12])([F:11])[F:10]>C1COCC1>[CH3:7][C@@H:8]([NH:13][C:14]1[S:15][CH:16]=[C:17]([C:19]2[CH:26]=[CH:25][C:22]([CH2:23][NH2:24])=[CH:21][CH:20]=2)[N:18]=1)[C:9]([F:10])([F:12])[F:11]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 86624159(R)-4-[2-(1-Methyl-2,2,2-trifluoroethylamino)-thiazol-4-yl]-benzonitrile

Product 1

HCID 59828830(R)-4-[2-(1-Methyl-2,2,2-trifluoroethylamino)-thiazol-4-yl]-benzylamineYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Add a solution of 1M lithium aluminum hydride in THF (12 mL, 12 mmol) dropwise to an ice-cooled solution of (R)-4-[2-(1-methyl-2,2,2-trifluoroethylamino)-thiazol-4-yl]-benzonitrile in anhydrous THF (10 mL). Heat to reflux for 1 h, cool to room temperature, quench by slow addition of water (12 mL), ether (50 mL), 1N NaOH (12 mL) and additional water (36 mL). Add EtOAc (50 mL), stir vigorously for 20 min and filter over a bed of Celite®. Dry the organic phase over MgSO4, filter and concentrate in vacuo to obtain the title compound (765 mg, 64%). MS (ES+) m/z: 302 (M+H)+.

Workup

  1. temperatureHeat
  2. temperatureto reflux for 1 h
  3. customquench by slow addition of water (12 mL), ether (50 mL), 1N NaOH (12 mL) and additional water (36 mL)
  4. filtrationfilter over a bed of Celite®
  5. dry with materialDry the organic phase over MgSO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-518555e7399a4df282d3260dc20c0cd4
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

Loading…