Tetrahydrofuran → 6-Cyclopentyl-5-methyl-nicotinic acid isopropyl ester

HRID 1908779Notes

Reaction equation

HRID 1908779 reaction equation
[CH:1]([O:4][C:5](=[O:14])[C:6]1[CH:11]=[C:10]([CH3:12])[C:9](Cl)=[N:8][CH:7]=1)([CH3:3])[CH3:2].[CH2:15]1[CH2:19]O[CH2:17][CH2:16]1.O1CCOC[CH2:21]1>>[CH:1]([O:4][C:5](=[O:14])[C:6]1[CH:11]=[C:10]([CH3:12])[C:9]([CH:15]2[CH2:19][CH2:21][CH2:17][CH2:16]2)=[N:8][CH:7]=1)([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 312751,4-DioxaneHCID 866505246-Chloro-5-methylnicotinic acid isopropyl ester

Product 1

HCID 670269086-Cyclopentyl-5-methyl-nicotinic acid isopropyl ester

Conditions

Temperature
75 °C

Procedure

Under argon, Pd(dppf) (11 mg, 14 μmol) is added to a solution of 6-chloro-5-methyl-nicotinic acid isopropyl ester (300 mg, 1.40 mmol) in dioxane (60 mL). To this mixture, a 0.5 M solution of cyclopentyl zink chloride in THF (452 mg, 2.11 mmol, 4.2 mL) is added dropwise. The mixture is stirred at 75° C. for 18 h before it is cooled to rt and quenched with water. The mixture is further diluted with water and extracted twice with EA (100 mL). The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified on prep. TLC plates with heptane:EA 1:1 to give 6-cyclopentyl-5-methyl-nicotinic acid isopropyl ester (138 mg) as a pale yellow oil; LC-MS: tR=0.91 min; [M+1]+=248.53.

Workup

  1. temperatureis cooled to rt
  2. customquenched with water
  3. additionThe mixture is further diluted with water
  4. extractionextracted twice with EA (100 mL)
  5. dry with materialextracts are dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product is purified on prep

Sources & evidence

ORD record
ord-e07c974fe81342679568f24358801085
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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