Hydrochloric Acid → Diethyl[(6-amino-5-methoxypyridin-3-yl)methyl]phosphonate

HRID 1948121

Reaction equation

HRID 1948121 reaction equation
[N+:1]([C:4]1[C:9]([O:10][CH3:11])=[CH:8][CH:7]=[CH:6][N:5]=1)([O-])=O.Cl[CH2:13][P:14](=[O:21])([O:18][CH2:19][CH3:20])[O:15][CH2:16][CH3:17].C(O[Na])(C)(C)C.Cl>CS(C)=O>[CH2:16]([O:15][P:14]([CH2:13][C:7]1[CH:6]=[N:5][C:4]([NH2:1])=[C:9]([O:10][CH3:11])[CH:8]=1)(=[O:21])[O:18][CH2:19][CH3:20])[CH3:17]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 76633Phosphonic acid, P-(chloromethyl)-, diethyl esterHCID 5560633-Methoxy-2-nitropyridineHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 86654065Diethyl[(6-amino-5-methoxypyridin-3-yl)methyl]phosphonateYield 19.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

A solution of 2-nitro-3-methoxypyridine (300 mg, 1.95 mmol) and diethyl chloromethylphosphonate (363 mg, 1.95 mmol) in DMSO (4 mL) was added dropwise to vigorously stirred solution of t-BuONa (0.561 g, 5.84 mmol) in DMSO (4 mL) at room temperature. The reaction mixture turned to deep orange immediately. Stirring was continued for 30 min, then the mixture was poured into 1 M HCl (aq) (10 mL). The product was extracted into ether (3×30 mL), dried over MgSO4, concentrated, and purified by silica gel chromatography (3% MeOH in DCM) to afford 102.6 mg of diethyl[(6-amino-5-methoxypyridin-3-yl)methyl]phosphonate (yield: 17%). 1H NMR (CD3OD, 400 MHz): δ=1.30 (t, J=6.8 Hz, 6H), 3.45 (d, J=22.4 Hz, 2H), 4.00 (s, 3H), 4.09-4.17 (m, 4H), 7.79 (t, J=2.4 Hz, 1H), 7.97 (t, J=2.4 Hz, 1H). MS (ES+): m/z 305.07 [MH+]. HPLC: tR=1.17 min (UPLC TOF, polar—3 min).

Workup

  1. extractionThe product was extracted into ether (3×30 mL)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. custompurified by silica gel chromatography (3% MeOH in DCM)

Sources & evidence

ORD record
ord-38df4a388e804322a0c06b393ec59d54
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Linked notes

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