Aluminium lithium hydride → 2-(4-(5-Trifluoromethyl-2-pyridinyloxy)phenyl)ethylamine

HRID 474730Notes

Reaction equation

HRID 474730 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[N+:7]([CH:10]=[CH:11][C:12]1[CH:28]=[CH:27][C:15]([O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][N:18]=2)=[CH:14][CH:13]=1)([O-])=O>O1CCCC1>[F:25][C:23]([F:24])([F:26])[C:20]1[CH:21]=[CH:22][C:17]([O:16][C:15]2[CH:27]=[CH:28][C:12]([CH2:11][CH2:10][NH2:7])=[CH:13][CH:14]=2)=[N:18][CH:19]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 677734032-[4-(2-Nitro-vinyl)-phenoxy]-5-trifluoromethyl-pyridine

Product 1

HCID 167707892-(4-(5-Trifluoromethyl-2-pyridinyloxy)phenyl)ethylamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Entire reaction was performed under argon atmosphere using syringe septa technique. To a stirred suspension of LiAlH4 (3.062 mmol, 2.5 eq) in dry tetrahydrofurane (20 ml) was added 2-[4-(2-nitro-vinyl)-phenoxy]-5-trifluoromethyl-pyridine (1.225 mmol, 1 eq) dissolved in dry tetrahydrofurane (10 ml) dropwise. Reaction mixture was stirred at rt for 2 h. Reaction mixture was quenched with 0.5 ml water. Celite and NaOH (3 ml, 5 N) were added and the mixture was filtered through Celite, rinsing the filter cake well with ether and DCM. Solvents were evaporated till dry. Crude product was purified on Biotage SP1 Snap Si 25; 25 ml/min in the gradient of MeOH in DCM: 0-5% for 3CV then from 5-40% for 30 CV. The appropriate fractions were combined and evaporated in vacuo to give the required product 2-[4-[5-trifluoromethyl-pyridin-2-yloxy)phenyl]-ethylamine s yellow oil (0.443 mmol, yield=36%, purity=91%). [M+H]+=283.30 1H NMR (300 MHz, DMSO-d6) δ/ppm 2.68 (d, 2H), 2.79 (d, J=7.5 Hz, 2H), 7.06-7.13 (m, 2H), 7.19 (d, J=8.7 Hz, 1H), 7.23-7.29 (m, 2H), 8.17-8.20 (m, 1H), 8.20-8.23 (m, 1H), 8.51-8.57 (m, 2H)

Workup

  1. customEntire reaction
  2. customReaction mixture
  3. customReaction mixture
  4. customwas quenched with 0.5 ml water
  5. additionCelite and NaOH (3 ml, 5 N) were added
  6. filtrationthe mixture was filtered through Celite
  7. washrinsing the filter cake well with ether and DCM
  8. customSolvents were evaporated
  9. customtill dry
  10. customCrude product was purified on Biotage SP1 Snap Si 25
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-8db9c8cf17df48909286a4f01011c706
Source dataset
uspto-grants-2014_01
Patent number
US08637536B2

Reaction notes

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