Methyl 1-(4-(2-(5-bromopyridin-2-yl)ethynyl)-3-fluorobenzyl)azetidine-3-carboxylate → Benzyl 1-(4-(2-(5-benzylpyridin-2-yl)ethynyl)-3-fluorobenzyl)azetidine-3-carboxylate

HRID 658984Notes

Reaction equation

HRID 658984 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]#[C:9][C:10]2[CH:24]=[CH:23][C:13]([CH2:14][N:15]3[CH2:18][CH:17]([C:19]([O:21][CH3:22])=[O:20])[CH2:16]3)=[CH:12][C:11]=2[F:25])=[N:6][CH:7]=1.[Br-].[CH2:27]([Zn+])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C1COCC1>[CH2:27]([C:2]1[CH:3]=[CH:4][C:5]([C:8]#[C:9][C:10]2[CH:24]=[CH:23][C:13]([CH2:14][N:15]3[CH2:18][CH:17]([C:19]([O:21][CH2:22][C:10]4[CH:24]=[CH:23][CH:13]=[CH:12][CH:11]=4)=[O:20])[CH2:16]3)=[CH:12][C:11]=2[F:25])=[N:6][CH:7]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

4

Reactant 2

HCID 57625189Methyl 1-(4-(2-(5-bromopyridin-2-yl)ethynyl)-3-fluorobenzyl)azetidine-3-carboxylateHCID 178419772HCID 178419772, compound3×

Product 1

HCID 57625188Benzyl 1-(4-(2-(5-benzylpyridin-2-yl)ethynyl)-3-fluorobenzyl)azetidine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

Methyl 1-(4-(2-(5-bromopyridin-2-yl)ethynyl)-3-fluorobenzyl)azetidine-3-carboxylate (340.0 mg, 843 μmol), PdCl2(P(t-Bu)2Ph)2 (37 mg, 59 μmol), and THF (4.0 mL) were combined under an argon atmosphere. Benzylzinc(II) bromide (0.5M in THF; 1.92 mL, 961 μmol) was added via syringe, and the resulting solution was stirred at 25° C. for 1 h. Additional benzylzinc(II) bromide (0.5M in THF; 1.92 mL) was then added, and the resulting solution was stirred for 1 h at 25° C. A third portion of benzylzinc(II) bromide (0.5M in THF; 1.92 mL) was then added, and the resulting solution was stirred for 1 h at 25° C. The mixture was subsequently partitioned between half-saturated aqueous NaHCO3 (50 mL) and EtOAc (100 mL). The organic layer was separated, washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-100% EtOAc/Hexanes) separately furnished benzyl 1-(4-(2-(5-benzylpyridin-2-yl)ethynyl)-3-fluorobenzyl)azetidine-3-carboxylate (MS (ESI) m/z: Calculated: 490.2; Observed: 490.8 (M++1)) and methyl 1-(4-(2-(5-benzylpyridin-2-yl)ethynyl)-3-fluorobenzyl)azetidine-3-carboxylate (MS (ESI) m/z: Calculated: 414.2; Observed: 414.8 (M++1)) as a yellow oils.

Workup

  1. stirringthe resulting solution was stirred for 1 h at 25° C
  2. stirringthe resulting solution was stirred for 1 h at 25° C
  3. customThe mixture was subsequently partitioned between half-saturated aqueous NaHCO3 (50 mL) and EtOAc (100 mL)
  4. customThe organic layer was separated
  5. washwashed with brine (30 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customChromatographic purification of the residue (silica gel, 0-100% EtOAc/Hexanes) separately furnished benzyl 1-(4-(2-(5-benzylpyridin-2-yl)ethynyl)-3-fluorobenzyl)azetidine-3-carboxylate (MS (ESI) m/z: Calculated: 490.2; Observed: 490.8 (M++1)) and methyl 1-(4-(2-(5-benzylpyridin-2-yl)ethynyl)-3-fluorobenzyl)azetidine-3-carboxylate (MS (ESI) m/z: Calculated: 414.2; Observed: 414.8 (M++1)) as a yellow oils

Sources & evidence

ORD record
ord-796a307119d049aebc9e8d84b4c8fa89
Source dataset
uspto-grants-2011_12
Patent number
US08080542B2

Reaction notes

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