Diglyme → 4-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidine

HRID 1670193Notes

Reaction equation

HRID 1670193 reaction equation
COC1C=C(OC)C=C(OC)C=1C[NH:6][C:7]1[CH:12]=[C:11](Cl)[N:10]=[CH:9][N:8]=1.[F:22][C:23]1[CH:28]=[C:27]([N+:29]([O-:31])=[O:30])[CH:26]=[CH:25][C:24]=1[OH:32].COCCOCCOC>O>[F:22][C:23]1[CH:28]=[C:27]([N+:29]([O-:31])=[O:30])[CH:26]=[CH:25][C:24]=1[O:32][C:11]1[N:10]=[CH:9][N:8]=[C:7]([NH2:6])[CH:12]=1

Participants

5

Reactant 3

HCID 8150DiglymeHCID 98252-Fluoro-4-nitrophenolHCID 59852864HCID 59852864, compound

Product 1

HCID 231530124-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidineYield 31%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of N-(2,4,6-trimethoxybenzyl)-6-chloropyrimidin-4-amine (2.2 g, 7.11 mmol), 2-fluoro-4-nitrophenol (1.1 g, 7.0 mmol), and 2-methoxyethyl ether (50 mL) was heated at 160° C. for 60 h. The reaction mixture was cooled to RT and poured into H2O (200 mL). The solid was collected, washed with 2 M aqueous Na2CO3 and H2O, and then vacuum dried on a Büchner funnel. The crude product was treated with TFA (20 mL) in dioxane (40 mL) and stirred at RT for 4 h. The reaction mixture was concentrated, the residue partitioned between EtOAc and saturated NaHCO3 solution. The EtOAc phase was separated, dried (MgSO4), concentrated and the crude product purified by flash chromatography using 1-2% MeOH in CH2Cl2 as the eluent to give 6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-amine (440 mg, 31%). 1H NMR (DMSO-d6) δ 8.31 (dd, 1H, J=10.4, 2.5 Hz), 8.14 (dd, 1H, J=9.8, 2.0 Hz), 8.04 (s, 1H), 7.61 (dd, 1H, J=8.3, 8.3 Hz), 7.07 (s, 2H), 6.02 (s, 1H); MS (ESI+) m/z 251.15 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. customThe solid was collected
  3. washwashed with 2 M aqueous Na2CO3 and H2O
  4. customvacuum dried on a Büchner funnel
  5. additionThe crude product was treated with TFA (20 mL) in dioxane (40 mL)
  6. concentrationThe reaction mixture was concentrated
  7. customthe residue partitioned between EtOAc and saturated NaHCO3 solution
  8. customThe EtOAc phase was separated
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. customthe crude product purified by flash chromatography

Sources & evidence

ORD record
ord-39b6f361f9b14491a276c4f591c5184f
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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