Aluminium lithium hydride → [2-Pyrrolidin-1-yl-6-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methanamine

HRID 1479834Notes

Reaction equation

HRID 1479834 reaction equation
[N:1]1([C:6]2[CH:11]=[C:10]([C:12]#[N:13])[CH:9]=[C:8]([C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C(OCC)C>[N:1]1([C:6]2[CH:11]=[C:10]([CH2:12][NH2:13])[CH:9]=[C:8]([C:14]3[CH:15]=[CH:16][C:17]([O:20][C:21]([F:24])([F:22])[F:23])=[CH:18][CH:19]=3)[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 903913072-Pyrrolidin-1-yl-6-[4-(trifluoromethoxy)phenyl]pyridine-4-carbonitrile

Product 1

HCID 131736589[2-Pyrrolidin-1-yl-6-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methanamineYield 78.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of nitrile 26C (1.1 g, 3.3 mmol) in diethyl ether (30 mL) was added in small amounts to a mixture of LiAlH4 (0.25 g, 2 mol eq) in diethyl ether (30 mL) stirred at 0° C. After the addition was completed, the mixture was stirred at room temperature overnight. The excess of LiAlH4 was destroyed at 0° C. by addition of small amount of water (30 mL), the solid formed was filtered off and the organic filtrate was separated, washed with brine (50 mL) and dried over Na2SO4. The organic phase was evaporated under reduced pressure and the residue was purified by flash chromatography (7:3 EtOAc:MeOH) to afford 27C as a pale yellow oil (0.87 g, 77% yield). 1HNMR (DMSO, 400 MHz) δ 1.97 (m, 4H), 3.48 (m, 4H), 3.68 (s, 2H), 4.15 (bs, 2H), 6.44 (s, 1H), 7.15 (s, 1H), 7.43 (d, 2H, J=8), 8.17 (d, 2H, J=8).

Workup

  1. additionAfter the addition
  2. stirringthe mixture was stirred at room temperature overnight
  3. customThe excess of LiAlH4 was destroyed at 0° C. by addition of small amount of water (30 mL)
  4. customthe solid formed
  5. filtrationwas filtered off
  6. customthe organic filtrate was separated
  7. washwashed with brine (50 mL)
  8. dry with materialdried over Na2SO4
  9. customThe organic phase was evaporated under reduced pressure
  10. customthe residue was purified by flash chromatography (7:3 EtOAc:MeOH)

Sources & evidence

ORD record
ord-de4b9a4247644b5a9bad8871ad9fb11e
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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