Sodium Hydroxide → 2-(5-Amino-3-(trifluoromethyl)pyridin-2-yl)-2-methylpropanenitrile

HRID 576211Notes

Reaction equation

HRID 576211 reaction equation
O.O.[Sn](Cl)Cl.[CH3:6][C:7]([C:11]1[C:16]([C:17]([F:20])([F:19])[F:18])=[CH:15][C:14]([N+:21]([O-])=O)=[CH:13][N:12]=1)([CH3:10])[C:8]#[N:9].[OH-].[Na+]>CC(=O)OCC>[NH2:21][C:14]1[CH:15]=[C:16]([C:17]([F:20])([F:18])[F:19])[C:11]([C:7]([CH3:10])([CH3:6])[C:8]#[N:9])=[N:12][CH:13]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 61436Stannous chloride dihydrateHCID 904165742-Methyl-2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)propanenitrile

Product 1

HCID 904159142-(5-Amino-3-(trifluoromethyl)pyridin-2-yl)-2-methylpropanenitrileYield 40.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Tin(II) chloride dihydrate (449 mg, 1.991 mmol) was added to a solution of 2-methyl-2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)propanenitrile (129 mg, 0.498 mmol) in EA (15 mL). The mixture was at 60° C. for 4 h. Then the solution was adjusted to pH=8-9 with 2N NaOH. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by preparative HPLC (MeCN/H2O as eluants, basic condition) to yield a white solid of 2-(5-amino-3-(trifluoromethyl)pyridin-2-yl)-2-methylpropanenitrile (46.48 mg, 0.203 mmol, 40.7% yield). TLC (PE/EA=1:1, Rf=0.3): 1H NMR (400 MHz, DMSO-d6) δ 8.04-8.17 (m, 1H), 7.31 (d, J=2.43 Hz, 1H), 5.97 (s, 2H), 1.70 (s, 6H); ES-LCMS m/z 230.1 (M+H).

Workup

  1. extractionThe combined organic extract
  2. washwas washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by preparative HPLC (MeCN/H2O as eluants, basic condition)

Sources & evidence

ORD record
ord-e7fbda47b5f1452ba682c504f5677bc5
Source dataset
uspto-grants-2015_05
Patent number
US09035063B2

Reaction notes

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