2-Methoxyethanol → 6-Amino-4-(2-methoxyethoxy)nicotinonitrile

HRID 1777865Notes

Reaction equation

HRID 1777865 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:11][O:12][CH2:13][CH2:14][OH:15].[NH2:16][C:17]1[CH:24]=[C:23](F)[C:20]([C:21]#[N:22])=[CH:19][N:18]=1>C1COCC1>[NH2:16][C:17]1[CH:24]=[C:23]([O:15][CH2:14][CH2:13][O:12][CH3:11])[C:20]([C:21]#[N:22])=[CH:19][N:18]=1

Participants

5

Reactant 3

HCID 80192-MethoxyethanolHCID 3251421Potassium bis(trimethylsilyl)amideHCID 1180369016-Amino-4-fluoronicotinonitrile2×

Product 1

HCID 1180368416-Amino-4-(2-methoxyethoxy)nicotinonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of KHMDS in THF (1 M, 48.1 ml, 48.1 mmol) was added to a solution of 2-methoxy ethanol (1.68 g, 21.88 mmol) in THF (90 ml) at room temperature. After 2 minutes 6-amino-4-fluoronicotinonitrile (intermediate 21, 3.00 g, 21.9 mmol) was added and the reaction mixture stirred for 16 h at room temperature. The reaction mixture was partitioned between saturated aqueous NH4Cl and EtOAc, extracted with EtOAc (2×), the combined EtOAc layers were washed with brine, dried over MgSO4 and evaporated. The residue was triturated with EtOAc and the title compound obtained by filtration as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 1H), 6.91 (s, br, 2H), 6.03 (s, 1H), 4.19-4.13 (m, 2H), 3.34-3.28 (m, 2H), 2.51 (s, 3H).

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous NH4Cl and EtOAc
  2. extractionextracted with EtOAc (2×)
  3. washthe combined EtOAc layers were washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe residue was triturated with EtOAc

Sources & evidence

ORD record
ord-8a05f10a65df4e8894f9d4b358513a7f
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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