Cesium fluoride → 3-[3-[2-(Benzyloxy)ethyl]phenyl]-5-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]pyridine

HRID 2095333Notes

Reaction equation

HRID 2095333 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([Sn](C)(C)C)[CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:24]([O:31][CH2:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36](I)[CH:35]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[F-].[Cs+]>[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[CH2:24]([O:31][CH2:32][CH2:33][C:34]1[CH:35]=[C:36]([C:18]2[CH:17]=[N:16][CH:15]=[C:14]([O:13][CH2:12][C@@H:9]3[CH2:10][CH2:11][N:8]3[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH:19]=2)[CH:37]=[CH:38][CH:39]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 105744715-Iodo-A-85380, 5-trimethylstannyl N-boc derivativeHCID 593713811-[2-(Benzyloxy)ethyl]-3-iodobenzene

Product 1

HCID 593714993-[3-[2-(Benzyloxy)ethyl]phenyl]-5-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]pyridineYield 58.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

3-[[1-(tert-Butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-(trimethylstannyl)pyridine (619 mg, 1.45 mmol), 1-[2-(benzyloxy)ethyl]-3-iodobenzene (490 mg, 1.45 mmol), and anhydrous DMF (5.0 mL) were placed in a 25 mL round-bottom flask with magnetic stirrer. To this mixture were rapidly added CsF (441 mg, 2.90 mmol, 2.0 equiv.), CuI (27.5 mg, 0.14 mmol, 0.10 equiv.), and Pd(PPh3)4 (84 mg, 0.07 mmol, 0.05 equiv.). The flask was fitted with a three-way stopcock with nitrogen balloon, and the atmosphere was exchanged three times. The reaction mixture was heated at 50° C. for 5 h. TLC analysis of the crude reaction mixture indicated that the aryl iodide was absent. After evaporation of the solvent in vacuo, the residue was chromatographed on silica gel with EtOAc/petroleum ether/Et3N 2:4:0.05 to give the title compound (400 mg, 58%) as a colorless oil. LC-MS (ESI) m/z 475 (M+H+).

Workup

  1. customThe flask was fitted with a three-way stopcock with nitrogen balloon
  2. customTLC analysis of the crude reaction mixture
  3. customAfter evaporation of the solvent in vacuo
  4. customthe residue was chromatographed on silica gel with EtOAc/petroleum ether/Et3N 2:4:0.05

Sources & evidence

ORD record
ord-457e1bc0a80e4f199eb8628ceef3f3a3
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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