1-(4-Chlorophenyl)pyrrolidine-3-carboxylic acid → 1-[1-(4-Chlorophenyl)-pyrrolidin-3-yl]-pent-4-en-1-one

HRID 579562Notes

Reaction equation

HRID 579562 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][CH:10]([C:13]([OH:15])=O)[CH2:9]2)=[CH:4][CH:3]=1.CO[N-]C>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:12][CH2:11][CH:10]([C:13](=[O:15])[CH2:4][CH2:3][CH:2]=[CH2:7])[CH2:9]2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 510638331-(4-Chlorophenyl)pyrrolidine-3-carboxylic acidHCID 53630747Methoxy-methyl amide

Product 1

HCID 668335781-[1-(4-Chlorophenyl)-pyrrolidin-3-yl]-pent-4-en-1-oneYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1-(4-chlorophenyl)-pyrrolidine-3-carboxylic acid and methoxy-methyl amide (1.1 g, 4.1 mmol) in tetrahydrofuran (20 mL) was cooled to 0° C. while maintaining the solution under an at mosphere of nitrogen. To the cold solution was added a THF solution of 4-butenylmagnesium bromide (0.5M in THF, 16.4 mL, 8.2 mmol) in a dropwise manner. After stirring for 1 hour the bath was removed and stirring was continued overnight. The resulting solution was poured into water, acidified to pH 3-4 with 1 N hydrochloric acid and extracted with ethyl acetate (3×). The combined organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated. Purification of the crude by flash column chromatography (silica gel, 0-25% ethyl acetate in heptane) gave the title compound as a colorless oil (940 mg, 87%); 1H NMR (CDCl3, 300 MHz) δ 7.15 (d, J=9 Hz, 2H), 6.46 (d, J=9 Hz, 2H), 5.81 (m, 1H), 5.12 (m, 2H), 3.54 (m, 2H), 3.26-3.39 (m, 3H), 2.62 (m, 2H), 2.36 (m, 2H) and 2.12-2.26 (m, 2H).

Workup

  1. temperaturewhile maintaining the solution under an at mosphere of nitrogen
  2. customwas removed
  3. stirringstirring
  4. waitwas continued overnight
  5. additionThe resulting solution was poured into water
  6. extractionextracted with ethyl acetate (3×)
  7. washThe combined organic phase was washed with saturated aqueous sodium chloride
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification of the crude by flash column chromatography (silica gel, 0-25% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-e020f0f87f08441e9f241d14ce1a2611
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

Loading…