2-Chloro-5-fluoropyrimidine → HCID 21919363, compound

HRID 1244432Notes

Reaction equation

HRID 1244432 reaction equation
Br[CH:2]([CH3:9])[CH2:3][CH:4]1[O:8][CH2:7][CH2:6][O:5]1.Cl[C:11]1[N:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=1>O1CCCC1.[Zn]>[O:5]1[CH2:6][CH2:7][O:8][CH:4]1[CH2:3][CH:2]([C:11]1[N:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=1)[CH3:9]

Participants

5

Reactant 2

HCID 5834662-Chloro-5-fluoropyrimidineHCID 219193922-(2-Bromopropyl)-1,3-dioxolane

Product 1

HCID 21919363HCID 21919363, compoundYield 22.9%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
40 °C

Procedure

To a stirring suspension of activated “Rieke” zinc in tetrahydrofuran (21 ml, 1.53M) was added 2-(2-bromopropyl)-1,3-dioxolane (6.6 g) in tetrahydrofuran (50 ml), a rise in temperature from 21° C. to 40° C. was observed, heated at 40° C. for 1 hour then allowed to cool to ambient temperature before adding 2-chloro-5-fluoropyrimidine (3 g) and [1,2-Bis(diphenylphosphino)-propane]dichloronickel(II)chloride (368 mg). The mixture was stirred at ambient temperature for 4 hours then filtered through a pad of celite and the filtrate evaporated under reduced pressure. Flash chromatography (silica gel, haxane-25% ethyl acetate in hexanes) then gave the product as a pale yellow oil (1.1 g); 1H NMR (d6-DMSO): 8.81 (s, 2H), 4.73 (dd, 1H), 3.66–3.87 (m, 4H), 3.21–3.30 (m, 1H), 2.19 (ddd, 1H), 1.83 (ddd, 1H), 1.27(d, 3H); m/z 213 (M+1).

Workup

  1. additionTo a stirring suspension
  2. customfrom 21° C. to 40° C.
  3. temperatureto cool to ambient temperature
  4. filtrationthen filtered through a pad of celite
  5. customthe filtrate evaporated under reduced pressure

Sources & evidence

ORD record
ord-23e926e6dab54b61b15c3a23a63adc63
Source dataset
uspto-grants-2006_10
Patent number
US07122551B2

Reaction notes

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