Diisopropylamine → 5-Ethyl-2-fluoro-3-pyridinecarboxaldehyde

HRID 2358316Notes

Reaction equation

HRID 2358316 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([C:15]1[CH:16]=[CH:17][C:18]([F:21])=[N:19][CH:20]=1)[CH3:14].[O:22]1CCC[CH2:23]1>>[CH2:13]([C:15]1[CH:16]=[C:17]([CH:23]=[O:22])[C:18]([F:21])=[N:19][CH:20]=1)[CH3:14]

Participants

5

Reactant 4

HCID 7912DiisopropylamineHCID 8028TetrahydrofuranHCID 210304025-Ethyl-2-fluoropyridineHCID 178418339Butyllithium

Product 1

HCID 860856655-Ethyl-2-fluoro-3-pyridinecarboxaldehyde

Procedure

A solution of diisopropylamine (1.01 mL, 7.19 mmol) in tetrahydrofuran (20 mL) was treated in ice-bath with n-butyllithium (2.5M, 2.9 mL, 7.19 mmol) and stirred for 30 min. The resulting solution was reacted at −78° C. with 5-ethyl-2-fluoropyridine (2-b, 0.75 g, 5.99 mmol), stirred for 4 h, and treated with N,N-dimethylfornmamide (482 mg, 6.59 mmol). The reaction mixture was quenched with acetic acid (1 mL), partitioned between ethyl acetate and water. The organic layer washed with 0.5N—HCl and then with brine, separated, dried (MgSO4) and concentrated in vacuo. Chromatography (30% ethyl acetate in hexanes) afforded the desired compound (2-f); 1H NMR (500 MHz, CDCl3) δ10.3 (s, 1 H), 8.29 (d, 1 H, J=2.0 Hz), 8.12 (dd, 1 H, J=9.0, 2.5 Hz), 2.73 (q, 2 H, J=7.8 Hz), 1.29 (t, 3 H, J=7.5 Hz).

Workup

  1. stirringstirred for 4 h
  2. additiontreated with N,N-dimethylfornmamide (482 mg, 6.59 mmol)
  3. customThe reaction mixture was quenched with acetic acid (1 mL)
  4. custompartitioned between ethyl acetate and water
  5. washThe organic layer washed with 0.5N—HCl
  6. customwith brine, separated
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6f3b594c2d874b3597d9efa3e6f041ff
Source dataset
uspto-grants-2010_07
Patent number
US07763659B2

Reaction notes

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