Cesium fluoride → 3-[[1-(tert-Butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-[3-(phenethoxymethyl)phenyl]pyridine

HRID 2095335Notes

Reaction equation

HRID 2095335 reaction equation
I[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][O:9][CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:3]=1.[C:18]([O:22][C:23]([N:25]1[CH2:28][CH2:27][C@H:26]1[CH2:29][O:30][C:31]1[CH:32]=[N:33][CH:34]=[C:35]([Sn](C)(C)C)[CH:36]=1)=[O:24])([CH3:21])([CH3:20])[CH3:19].[F-].[Cs+]>CN(C=O)C.[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>[C:18]([O:22][C:23]([N:25]1[CH2:28][CH2:27][C@H:26]1[CH2:29][O:30][C:31]1[CH:32]=[N:33][CH:34]=[C:35]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][O:9][CH2:10][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:3]=2)[CH:36]=1)=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 105744715-Iodo-A-85380, 5-trimethylstannyl N-boc derivativeHCID 593714071-Iodo-3-(phenethoxymethyl)benzene

Product 1

HCID 593715633-[[1-(tert-Butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-[3-(phenethoxymethyl)phenyl]pyridineYield 55%

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

A solution/suspension of 1-iodo-3-(phenethoxymethyl)benzene (300 mg, 0.89 mmol, 1.0 equiv.), 3-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-(trimethylstannyl)pyridine (380 mg, 0.89 mmol), CsF (271 mg, 1.78 mmol, 2.0 equiv.), CuI (17 mg, 0.09 mmol, 0.10 equiv.) and Pd(PPh3)4 (46 mg, 0.04 mmol, 0.05 equiv.) in anhydrous DMF (5 mL) was stirred for 5 h at 50° C. under nitrogen. The reaction progress was monitored by TLC (EtOAc/petroleum ether 1:1). The mixture was concentrated under vacuum, the residue was diluted with water and extracted with EtOAc (2×50 mL), and the combined organic layers were dried over Na2SO4. After concentration in vacuo, the residue was applied onto a silica gel column, which was eluted with EtOAc/petroleum ether/Et3N 3:6:0.5 to give the title compound (230 mg, 55%) as a yellow oil. 1H NMR (CDCl3, 300 MHz) δ 8.48 (s, 1H), 8.36 (d, J=2.1 Hz, 1H), 7.53-7.43 (m, 4H), 7.38 (s, 1H), 7.35-7.23 (m, 5H), 4.62 (s, 3H), 4.43 (s, 1H), 4.25 (dd, J=7.5, 3.0 Hz, 1H), 3.94 (t, J=7.5 Hz, 2H), 3.77 (t, J=7.5 Hz, 2H), 2.99 (t, J=7.2 Hz, 2H), 2.43-2.33 (m, 2H), 1.43 (s, 9H). LC-MS (ESI) m/z 475 (M+H+).

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. additionthe residue was diluted with water
  3. extractionextracted with EtOAc (2×50 mL)
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. concentrationAfter concentration in vacuo
  6. washwas eluted with EtOAc/petroleum ether/Et3N 3:6:0.5

Sources & evidence

ORD record
ord-bb932e75dcb74bf4b15f54588805b25b
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

Loading…