Acetaldehyde → HCID 70873937, compound

HRID 2208823Notes

Reaction equation

HRID 2208823 reaction equation
[CH3:1][C:2]1[C:7]([NH:8][CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[CH:6][N:5]=[CH:4][C:3]=1[C:15]([O:17][CH3:18])=[O:16].[CH:19](=O)[CH3:20].FC(F)(F)C(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.O>[CH2:19]([N:8]([CH:9]1[CH2:10][CH2:11][O:12][CH2:13][CH2:14]1)[C:7]1[C:2]([CH3:1])=[C:3]([C:15]([O:17][CH3:18])=[O:16])[CH:4]=[N:5][CH:6]=1)[CH3:20]

Participants

8

Reactant 5

HCID 177Acetaldehyde2×HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 70873824HCID 70873824, compound

Product 1

HCID 70873937HCID 70873937, compoundYield 62.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

To a stirred solution of methyl 4-methyl-5-[(oxan-4-yl)amino]pyridine-3-carboxylate (600 mg, 2.40 mmol) in DCE (20 ml) under a nitrogen atmosphere was added acetaldehyde (1.07 ml, 19.2 mmol) followed by trifluoroacetic acid (367 μl, 4.79 mmol) and the reaction was left to stir for 5 min before the addition of sodium triacetoxyborohydride (3.05 g, 14.4 mmol). The reaction was stirred for 16 h at room temperature after which time more acetaldehyde (500 μl) and sodium triacetoxyborohydride (1.0 g) were added and the reaction stirred for a further 16 h. Distilled water (20 ml) was added and solid NaHCO3 was added until pH8. The phases were separated and then the aqueous phase was washed with DCM (2×50 ml), the combined organics were washed with brine (50 ml), dried using Na2SO4, filtered and evaporated. The residue was purified using a 25 g Isolute silica column using a gradient of 0% to 50% EtOAc in heptane to afford the title compound as a pale yellow oil (418 mg, 60%). LC-MS 96%, m/z=279.1, 1H NMR (500 MHz, Chloroform-d) δ 8.76 (s, 1H), 8.44 (s, 1H), 3.97 (d, J=11.0 Hz, 2H), 3.93 (s, 3H), 3.33 (td, J=11.6, 2.1 Hz, 2H), 3.13 (q, J=7.1 Hz, 2H), 3.04 (tt, J=10.9, 4.0 Hz, 1H), 2.54 (s, 3H), 1.76-1.59 (m, 4H), 0.89 (t, J=7.1 Hz, 3H).

Workup

  1. waitthe reaction was left
  2. additionwere added
  3. customThe phases were separated
  4. washthe aqueous phase was washed with DCM (2×50 ml)
  5. washthe combined organics were washed with brine (50 ml)
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified

Sources & evidence

ORD record
ord-6b8214296c4748e8a51a99864727219f
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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