Triphenylphosphine → Methyl 4-(3-hydroxypropyl)pyridine-2-carboxylate

HRID 854002Notes

Reaction equation

HRID 854002 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[C:8](I)[CH:7]=[CH:6][N:5]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O:33][CH:34](OCC)[C:35]#[CH:36])C>[Cu]I.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(N(CC)CC)C>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[C:8]([CH2:36][CH2:35][CH2:34][OH:33])[CH:7]=[CH:6][N:5]=1)=[O:11]

Participants

7

Reactant 3

HCID 11776TriphenylphosphineHCID 662853,3-DiethoxypropyneHCID 22742038Methyl 4-iodopicolinate

Product 1

HCID 15928280Methyl 4-(3-hydroxypropyl)pyridine-2-carboxylate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 8471TriethylamineSolvent

Procedure

To a dry flask were added intermediate 11b prepared in general method P (2.98 g, 11.33 mmol, 1 equiv), triphenylphosphine (238 mg, 0.91 mmol, 0.08 equiv), copper(I) iodide (172.6 mg, 0.91 mmol, 0.08 equiv), palladium acetate (101.6 mg, 0.45 mmol, 0.04 equiv) and triethylamine (42 mL). The mixture was deaerated with nitrogen, followed by addition of 3,3-Diethoxy-propyne (Aldrich) (2.90 g, 22.7 mmol, 2 equiv). The mixture was stirred at rt for 3 h. The solvent was removed under vacuum to give a dark residue. The residue was purified by chromatography to give a yellow oil 11c (R9′=3,3-Diethoxy-prop-1-ynyl) (3 g, 100%): 1H NMR (300 MHz, CDCl3) δ 8.69 (dd, J=0.8, 5.0, 1), 8.15 (d, J=0.8, 1.4, 1), 7.49 (dd, J=1.7, 5.0, 1), 5.48 (s, 1), 3.99 (s, 3), 3.82-3.73 (m, 2), 3.71-3.62 (m, 2), 1.26 (t, J=7.2, 6). MS (ESPOS): 264.6 [M+H]+.

Workup

  1. customThe solvent was removed under vacuum
  2. customto give a dark residue
  3. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-525c520df601484985c75950f7901a2a
Source dataset
uspto-grants-2007_08
Patent number
US07256177B2

Reaction notes

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