Nitrogen → 2-Benzyl-4-methoxypyrimidine

HRID 1676294Notes

Reaction equation

HRID 1676294 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][N:3]=1.N#N.[Br-].[CH2:13]([Zn+])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:13]([C:2]1[N:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][N:3]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 947NitrogenHCID 5889352-Chloro-4-methoxypyrimidineHCID 178419772HCID 178419772, compound

Product 1

HCID 198462042-Benzyl-4-methoxypyrimidineYield 98%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-chloro -4-methoxypyrimidine (0.500 g, 3.46 mmol) and PdCl2(PPh3)2 (0.121 g, 0.173 mmol) in THF (10 mL) was sparged with N2. Benzylzinc(II) bromide (8.30 mL, 4.15 mmol; 0.5 M solution in THF) was added and the reaction mixture was stirred at reflux for 1 hour. The reaction mixture was cooled to room temperature and then partitioned between EtOAc and H2O. The phases were separated, and the aqueous phase was re-extracted with EtOAc (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude dark brown oil. The crude product was purified by flash column chromatography, eluting with 20:1 dichloromethane/EtOAc. The desired product (0.676 g, 98%) was obtained as a dark yellow oil. 1H NMR (400 MHz, CDCl3) δ8.34 (d, J=5.9 Hz, 1H), 7.41-7.25 (m, 4H), 7.21 (m, 1H), 6.53 (d, J=5.5 Hz, 1H), 4.16 (s, 2H), 3.95 (s, 3H). LRMS (ESI pos) m/e 201 (M+1).

Workup

  1. temperatureat reflux for 1 hour
  2. custompartitioned between EtOAc and H2O
  3. customThe phases were separated
  4. extractionthe aqueous phase was re-extracted with EtOAc (1×)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a crude dark brown oil
  9. customThe crude product was purified by flash column chromatography
  10. washeluting with 20:1 dichloromethane/EtOAc

Sources & evidence

ORD record
ord-19129e6d64a045a0b74b549f4e580b4d
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

Loading…