Tetrahydrofuran → 4-(but-3-enyl)-2-chloro-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine

HRID 474254Notes

Reaction equation

HRID 474254 reaction equation
[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:6]=2[N:7]=1.[CH2:18]1[CH2:22]O[CH2:20][CH2:19]1.C([Mg]Br)CC=C>CN1C(=O)CCC1>[CH2:20]([C:4]1[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:6]=2[N:7]=[C:2]([Cl:1])[N:3]=1)[CH2:19][CH:18]=[CH2:22]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 580754632,4-Dichloro-7-phenyl-6,7-dihydro-5H-cyclopenta[D]pyrimidineHCID 178418797HCID 178418797, compound2×

Product 1

HCID 866681064-(but-3-enyl)-2-chloro-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidineYield 51.2%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
-78 °C

Procedure

A 250 mL three-neck round bottom flask equipped with a refluxed condenser and nitrogen inlet was charged with 2,4-dichloro-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (2 g, 7.54 mmol), Fe(acac)2 (0.400 g, 1.131 mmol), THF (84 mL) and NMP (6.4 mL). The resulting solution was cooled to −78° C. and but-3-enyl magnesium bromide was added (20 mL) dropwise over twenty min. During the addition, the color of the reaction mixture changed from deep red to brown. After stirring for 1 h at −78° C., another 20 mL of but-3-enyl magnesium bromide was added and stirred for further 1 h. The reaction mixture was allowed to warm to 0° C. and quenched with saturated ammonium chloride solution (250 mL). It was then extracted with MTBE (2×200 mL), washed with brine (25 mL), dried over anhydrous sodium sulphate and concentrated in vacuo to get a crude brown oil. It was purified by a Teledyne Isco instrument using a 40 g silica column and 4-7% ethyl acetate in pet ether to get 4-(but-3-enyl)-2-chloro-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (1.1 g, 51.2%). LC-MS (M+H)+=285.2. 1H NMR (400 MHz, CDCl3) δ ppm 7.33-7.24 (3H, m), 7.14-7.12 (2H, m), 5.89-5.83 (1H, m), 5.09-5.00 (2H, m), 4.37 (1H, t, J=7.2 Hz), 3.04-3.01 (1H, m), 2.94-2.92 (1H, m), 2.85-2.81 (2H, m), 2.71-2.66 (1H, m), 2.55-2.51 (2H, m), 2.23-2.19 (1H, m).

Workup

  1. customA 250 mL three-neck round bottom flask equipped with a refluxed condenser and nitrogen inlet
  2. additionDuring the addition
  3. stirringstirred for further 1 h
  4. temperatureto warm to 0° C.
  5. customquenched with saturated ammonium chloride solution (250 mL)
  6. extractionIt was then extracted with MTBE (2×200 mL)
  7. washwashed with brine (25 mL)
  8. dry with materialdried over anhydrous sodium sulphate
  9. concentrationconcentrated in vacuo
  10. customto get a crude brown oil
  11. customIt was purified by a Teledyne Isco instrument

Sources & evidence

ORD record
ord-77b9dec9a0d34fd08dcad9979d66742a
Source dataset
uspto-grants-2014_01
Patent number
US08637523B2

Reaction notes

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