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

HRID 658983Notes

Reaction equation

HRID 658983 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](I)=[N:6][CH:7]=1.[C:9]([C:11]1[CH:25]=[CH:24][C:14]([CH2:15][N:16]2[CH2:19][CH:18]([C:20]([O:22][CH3:23])=[O:21])[CH2:17]2)=[CH:13][C:12]=1[F:26])#[CH:10]>C(N(CC)CC)C.CCOC(C)=O.[Cu]I.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>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:10]#[C:9][C:11]2[CH:25]=[CH:24][C:14]([CH2:15][N:16]3[CH2:19][CH:18]([C:20]([O:22][CH3:23])=[O:21])[CH2:17]3)=[CH:13][C:12]=2[F:26])=[N:6][CH:7]=1

Participants

7

Reactant 2

HCID 5936905-Bromo-2-iodopyridineHCID 25254788Methyl 1-(4-ethynyl-3-fluorobenzyl)azetidine-3-carboxylate

Product 1

HCID 57625189Methyl 1-(4-(2-(5-bromopyridin-2-yl)ethynyl)-3-fluorobenzyl)azetidine-3-carboxylate

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 5-bromo-2-iodopyridine (800 mg, 2818 μmol), methyl 1-(4-ethynyl-3-fluorobenzyl)azetidine-3-carboxylate (704 mg, 2846 μmol), and copper(I) iodide (21.5 mg, 113 μmol) in triethylamine (9.4 mL) was sparged with argon (30 sec), and PdCl2(PPh3)2 (79.1 mg, 113 μmol) was then added in one portion at 25° C. The reaction mixture was cooled to 0° C. and stirred for 40 min, and then allowed to stir at 25° C. for 1.5 h. The mixture was subsequently diluted with EtOAc (120 mL) and sequentially washed with water (4×30 mL) and brine (30 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-100% EtOAc/Hexanes) furnished methyl 1-(4-(2-(5-bromopyridin-2-yl)ethynyl)-3-fluorobenzyl)azetidine-3-carboxylate as a light yellow oil. MS (ESI) m/z: Calculated: 402.0/404.0; Observed: 402.8/404.8 (M++1).

Workup

  1. additionwas then added in one portion at 25° C
  2. stirringto stir at 25° C. for 1.5 h
  3. washsequentially washed with water (4×30 mL) and brine (30 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customChromatographic purification of the residue (silica gel, 0-100% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-418717bf9bf84a119eda644b1f6d57cf
Source dataset
uspto-grants-2011_12
Patent number
US08080542B2

Reaction notes

Loading…