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

HRID 2095337
Notes
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Reaction equation

HRID 2095337 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].I[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH2:32][CH2:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[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>[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]([C:29]2[CH:30]=[CH:25][CH:26]=[C:27]([O:31][CH2:32][CH2:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH:28]=2)[CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 105744715-Iodo-A-85380, 5-trimethylstannyl N-boc derivativeHCID 593716201-Iodo-3-(3-phenylpropoxy)benzene

Product 1

HCID 593716773-[[1-(tert-Butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-[3-(3-phenylpropoxy)phenyl]pyridine

Reagents, catalysts & solvents 3

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

Conditions

Temperature
50 °C

Procedure

3-[[1-(tert-Butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-(trimethylstannyl)pyridine (75 mg, 176 μmol), 1-iodo-3-(3-phenylpropoxy)benzene (59 mg, 174 μmol, 1.0 equiv.) and anhydrous DMF (2 mL) were placed in a 25 mL round-bottom flask with magnetic stirrer. To this mixture were added rapidly copper(I) iodide (3.3 mg, 0.02 mmol, 0.10 equiv.), cesium fluoride (53 mg, 0.35 mmol, 2.0 equiv.), and Pd(PPh3)4 (10.1 mg, 0.01 mmol, 0.05 equiv.). The flask was fitted with a three-way stopcock with nitrogen balloon, and the atmosphere was exchanged. The reaction mixture was heated at 50° C. for 6 h. The bulk of solvent was pumped off at room temperature with an oil pump. The reaction progress was monitored by TLC (EtOAc/petroleum ether 1:1). The residue was chromatographed on silica gel with EtOAc/petroleum ether/Et3N 2:3:0.05. This resulted in 55 mg (66%) of 3-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-[3-(3-phenylpropoxy)phenyl]pyridine as a colorless oil. 1H NMR (CDCl3, TMS, 300 MHz) δ 8.48 (s, 1H), 8.33 (s, 1H), 8.02 (s, 1H), 7.57 (br s, 1H), 7.39 (t, 1H, J=8.0 Hz), 7.34-7.19 (m, 4H), 7.16 (d, 1J, J=8.1 Hz), 7.10 (s, 1H), 6.96 (dd, 1H, J=2.1, 8.1 Hz), 4.55 (br m, 1H), 4.43 (br m, 1H), 4.22 (dd, 1H, J=2.5, 10.0 Hz), 4.04 (t, 2H, J=6.3 Hz), 3.91 (t, 2H, J=7.5 Hz), 2.85 (7, 2H, J=7.5 Hz), 2.36 (m, 2H), 2.15 (m, 3H), 1.41 (s, 9H).

Workup

  1. customThe flask was fitted with a three-way stopcock with nitrogen balloon
  2. customwas pumped off at room temperature with an oil pump
  3. customThe residue was chromatographed on silica gel with EtOAc/petroleum ether/Et3N 2:3:0.05
  4. customThis resulted in 55 mg (66%) of 3-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-[3-(3-phenylpropoxy)phenyl]pyridine as a colorless oil

Sources & evidence

ORD record
ord-ce948d156a974ccb8521bade3c823d6b
Source dataset
uspto-grants-2013_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08445684B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes