2-Bromopyrimidine → HCID 57803260, compound

HRID 2367014Notes

Reaction equation

HRID 2367014 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:18])[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C([Mg]Cl)(C)C.Br[C:25]1[N:30]=[CH:29][CH:28]=[CH:27][N:26]=1>C1COCC1.CCOC(C)=O.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Ni+2].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[N:26]1[CH:27]=[CH:28][CH:29]=[N:30][C:25]=1[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:18])[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 783452-BromopyrimidineHCID 578033098-(4-Iodo-phenyl)-1,4-dioxa-spiro[4.5]decan-8-olHCID 178418918HCID 178418918, compound

Product 1

HCID 57803260HCID 57803260, compoundYield 69.2%

Reagents, catalysts & solvents 4

HCID 812191,3-Bis(diphenylphosphino)propaneCatalystHCID 9834912Nickel(II) acetylacetonateCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 8-(4-iodo-phenyl)-1,4-dioxa-spiro[4.5]decan-8-ol (450.0 mg, 1.249 mmol) in THF (1.0 mL) at room temperature was added dropwise isopropylmagnesium chloride (2.0 M in THF, 1.37 mL) and the reaction mixture was stirred at room temperature for 30 mins. To another flask charged with nickel acetylacetonate (20 mg, 0.06 mmol) and 1,3-bis(diphenylphosphino)-propane (26 mg, 0.062 mmol) suspended in THF (3 mL) under N2 was added 2-bromopyrimidine (199 mg, 1.25 mmol). The resulting mixture was stirred at room temperature until it is clear. This mixture was transferred into the degassed Grignard solution prepared above. The resulting mixture was stirred at room temperature overnight. The reaction mixture was diluted with EtOAc, quenched with water, washed with brine, dried over Na2SO4, and concentrated. The residue was columned on silica gel, eluting with hexane/EtOAc (2/1), to gave the desired compound (270 mg, 69%) as a white solid. LCMS: 313.1, (M+H, 100%). 1H NMR (CDCl3): δ 8.86 (d, 2H), 8.46 (dd, 2H), 7.71 (dd, 2H), 7.24 (t, 1H), 4.05 (d, 4H), 2.30 (dt, 2H), 2.18 (dt, 2H), 1.90 (m, 2H), 1.78 (m, 2H).

Workup

  1. stirringThe resulting mixture was stirred at room temperature until it
  2. customprepared above
  3. stirringThe resulting mixture was stirred at room temperature overnight
  4. customquenched with water
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. washeluting with hexane/EtOAc (2/1)

Sources & evidence

ORD record
ord-4a1504e5f84a448abb08c7e3e13f066b
Source dataset
uspto-grants-2014_04
Patent number
US08697870B2

Reaction notes

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