Trifluoroacetic acid → HCID 70873824, compound

HRID 2208822Notes

Reaction equation

HRID 2208822 reaction equation
[NH2:1][C:2]1[C:3]([CH3:12])=[C:4]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[N:6][CH:7]=1.[O:13]1[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]1.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>[CH3:12][C:3]1[C:2]([NH:1][CH:16]2[CH2:17][CH2:18][O:13][CH2:14][CH2:15]2)=[CH:7][N:6]=[CH:5][C:4]=1[C:8]([O:10][CH3:11])=[O:9]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 121599Tetrahydro-4H-pyran-4-one2×HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 67248245HCID 67248245, compound

Product 1

HCID 70873824HCID 70873824, compoundYield 91.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

To a stirred solution of methyl 5-amino-4-methylpyridine-3-carboxylate (805 mg, 4.84 mmol) in DCE (20 ml) under a nitrogen atmosphere was added oxan-4-one (537 μl, 5.80 mmol) followed by trifluoroacetic acid (742 μl, 9.69 mmol) and the reaction was left to stir for 5 min before the addition of sodium triacetoxyborohydride (1.54 g, 7.27 mmol). The reaction was stirred for 16 h at room temperature after which time more oxan-4-one (100 μl) and sodium triacetoxyborohydride (300 mg) were added and the reaction stirred for a further 6 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 EtOAc (2×50 ml), the combined organics were washed with brine (50 ml), dried using Na2SO4, filtered and evaporated to afford the title compound as a pale yellow solid (1.11 g, 88%) which was used in the next stage without any further purification. LC-MS 96%, m/z=251.0, 1H NMR (500 MHz, Chloroform-d) δ 8.40 (s, 1H), 8.10 (s, 1H), 4.03 (dt, J=11.9, 3.5 Hz, 2H), 3.92 (s, 3H), 3.68-3.58 (m, 1H), 3.54 (tt, J=8.1, 4.1 Hz, 3H), 2.35 (s, 3H), 2.12-2.05 (m, 2H), 1.53 (ddd, J=23.8, 11.0, 4.3 Hz, 2H).

Workup

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

Sources & evidence

ORD record
ord-b6e441fbbef748fba39dd41c11f24095
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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