Sodium borohydride → (R)-4-[(1-Methyl-2,2,2-trifluoro-ethylamino)-methyl]-benzylamine

HRID 1191007Notes

Reaction equation

HRID 1191007 reaction equation
[CH3:1][C@@H:2]([NH:7][CH2:8][C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=1)[C:3]([F:6])([F:5])[F:4].[BH4-].[Na+]>CO.O.O.O.O.O.O.[Co](Cl)Cl>[CH3:1][C@@H:2]([NH:7][CH2:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][NH2:14])=[CH:15][CH:16]=1)[C:3]([F:5])([F:6])[F:4]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 59828823(R)-4-[(1-Methyl-2,2,2-trifluoro-ethylamino)-methyl]-benzonitrile

Product 1

HCID 59828891(R)-4-[(1-Methyl-2,2,2-trifluoro-ethylamino)-methyl]-benzylamineYield 57%

Reagents, catalysts & solvents 2

HCID 517166Dichlorocobalt hexahydrateCatalystHCID 887MethanolSolvent

Procedure

Add cobalt(II) chloride hexahydrate (1.45 g, 6.09 mmol) to a solution of (R)-4-[(1-methyl-2,2,2-trifluoro-ethylamino)-methyl]-benzonitrile (695 mg, 3.045 mmol) in methanol (20 mL). Add sodium borohydride (1.15 g, 30.45 mmol) in small batches and stir at room temperature for 3 h. Quench with water, add chloroform and filter the mixture through Celite®. Separate layers and extract the aqueous phase twice with chloroform. Dry the combined organic extracts over MgSO4, filter and concentrate in vacuo. Purify by chromatography on silica gel (40 g) eluting with a gradient of DCM to 19:1 and 9:1 DCM/(chloroform:methanol:concentrated NH4OH 80:18:2) to obtain the title compound as an oil (0.4 g, 57%). MS (ES+) m/z: 233 (M+H)+.

Workup

  1. customQuench with water
  2. additionadd chloroform
  3. filtrationfilter the mixture through Celite®
  4. extractionSeparate layers and extract the aqueous phase twice with chloroform
  5. dry with materialDry the combined organic extracts over MgSO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify by chromatography on silica gel (40 g)
  9. washeluting with a gradient of DCM to 19:1 and 9:1 DCM/(chloroform:methanol:concentrated NH4OH 80:18:2)

Sources & evidence

ORD record
ord-8ac68ba473c545fea86edb87522b3621
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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