1-Cyclopentyl-2-propen-1-ol → 3-(2-Chloro-5-ethoxy-pyridin-4-yl)-1-cyclopentyl-propan-1-one

HRID 2387167Notes

Reaction equation

HRID 2387167 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[C:5]([O:9][CH2:10][CH3:11])=[CH:4][N:3]=1.[CH:12]1([CH:17]([OH:20])[CH:18]=[CH2:19])[CH2:16][CH2:15][CH2:14][CH2:13]1.C([O-])(=O)C.[Na+]>CC(N(C)C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:19][CH2:18][C:17]([CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)=[O:20])[C:5]([O:9][CH2:10][CH3:11])=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 1451331-Cyclopentyl-2-propen-1-olHCID 517045Sodium AcetateHCID 534383202-Chloro-5-ethoxy-4-iodopyridine

Product 1

HCID 587641673-(2-Chloro-5-ethoxy-pyridin-4-yl)-1-cyclopentyl-propan-1-oneYield 80.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-chloro-5-ethoxy-4-iodo-pyridine (1.5 g, 5.3 mmol), 1-cyclopentyl-2-propen-1-ol (0.83 g, 6.61 mmol), sodium acetate (0.54 g, 6.6 mmol), palladium (II) acetate (24 mg, 0.11 mmol) in DMAC (10 mL) was heated to 90° C. under N2 for 16 hours. The reaction mixture was partitioned between 1N HCl and EtOAc. The organic layers were washed with saturated NaHCO3, brine, dried over MgSO4 and concentrated. Purification by silica gel chromatography (0% to 60% EtOAc in hexanes) gave the desired product (1.2 g, 58%). 1H NMR (300 MHz, CDCl3): δ 1.44 (t, J=7.0 Hz, 3H), 1.55-1.87 (m, 8 H), 2.75 (m, 2 H), 2.86 (m, 3 H), 4.11 (q, J=7.0 Hz, 2 H), 7.09 (s, 1 H), 7.89 (s, 1H).

Workup

  1. customThe reaction mixture was partitioned between 1N HCl and EtOAc
  2. washThe organic layers were washed with saturated NaHCO3, brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography (0% to 60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-07d7ad8a869b401b91888814c4e20652
Source dataset
uspto-grants-2012_09
Patent number
US08268835B2

Reaction notes

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