Dichloromethane → 5-Hexynyl-3-(2-(S)-azetidinylmethoxy)pyridine dihydrochloride

HRID 365833Notes

Reaction equation

HRID 365833 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:13][CH2:12][N:11]2C(OC(C)(C)C)=O)[CH:5]=[N:6][CH:7]=1.C(N(CC)CC)C.[CH:28]#[C:29][CH2:30][CH2:31][CH2:32][CH3:33].C(Cl)[Cl:35]>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.[Cu]I>[ClH:35].[ClH:35].[C:28]([C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:13][CH2:12][NH:11]2)[CH:5]=[N:6][CH:7]=1)#[C:29][CH2:30][CH2:31][CH2:32][CH3:33]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 127321-HexyneHCID 10688713(S)-Tert-butyl 2-(((5-bromopyridin-3-YL)oxy)methyl)azetidine-1-carboxylate

Product 1

HCID 98617545-Hexynyl-3-(2-(S)-azetidinylmethoxy)pyridine dihydrochlorideYield 56%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Procedure

To a solution of 5-bromo-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from Example 54b (180 mg, 0.48 mmol), bis(triphenylphosphine)palladium(II) chloride (7 mg, 0.05 mmol), copper (I) iodide (2 mg) and triethylamine (1.0 mL) in CH2Cl2 (3 mL) was added 1-hexyne (8.3 mL, 0.72 mmol). The mixture was refluxed overnight and cooled to room temperature. The solvent was removed, and the residue was chromatographed on a silica gel column, eluting with EtOAc:hexane 1:1 to afford the title compound (102 mg, 56% yield). MS (CI/NH3) m/z 379 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ0.96 (t, J=6.6 Hz, 3H), 1.43 (s, 9H), 1.46-1.69 (m, 4H), 2.20-2.40 (m, 2H), 2.44-2.56 (m, 2H), 3.83-3.92 (m, 2H), 4.06-4.15 (m, 1H), 4.26-4.38 (m, 1H), 4.45-4.57 (m, 1H), 7.34 (br s, 1H), 7.51-7.58 (m, 1H).

Workup

  1. temperatureThe mixture was refluxed overnight
  2. customThe solvent was removed
  3. customthe residue was chromatographed on a silica gel column
  4. washeluting with EtOAc:hexane 1:1

Sources & evidence

ORD record
ord-30dd755167144441b8dc391ae2c9f35d
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

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