Bromide ion → 1-(5'-chloro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-pent-4-en-1-one

HRID 579592Notes

Reaction equation

HRID 579592 reaction equation
CON(C)[C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5].[Br-].O.Cl>O1CCCC1>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([N:9]2[CH2:8][CH2:7][CH:6]([C:4](=[O:5])[CH2:8][CH2:7][CH:6]=[CH2:4])[CH2:11][CH2:10]2)=[N:13][CH:14]=1

Participants

6

Reactant 4

HCID 259Bromide ionHCID 313Hydrochloric AcidHCID 962WaterHCID 458195565'-chloro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid, methoxy-methyl-amide

Product 1

HCID 668334951-(5'-chloro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-pent-4-en-1-oneYield 185.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

While under a nitrogen atmosphere, a solution of 5′-chloro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carboxylic acid, methoxy-methyl-amide (1.0 g, 3.5 mmol), in tetrahydrofuran (10 mL) was cooled to 0° C. and treated with 4-butenylmagnesiun bromide (0.5 M in THF, 17.6 mL, 8.8 mmol) dropwise. After stirring for 1 hour at 0° C. and room temperature overnight the reaction mixture was poured into water, acidified to pH 3-4 with 1N 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 in vacuo. Purification by flash column chromatography (silica gel, 0-25% ethyl acetate in heptane) gave 1-(5′-chloro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-pent-4-en-1-one as a colorless oil (904 mg, 93%); 1H NMR (CDCl3, 300 MHz) δ 8.05 (d, J=2.5 Hz, 1H), 7.42 (dd, J1=9.0 Hz, J2=2.5 Hz, 1H), 6.62 (d, J=9.0 Hz, 1H), 5.80 (m, 1H), 5.04 (m, 2H), 4.23 (m, 2H), 2.92 (m, 2H), 2.59 (m, 3H), 2.36 (m, 2H), 1.98 (m, 2H) and 1.70 (m, 2H); MS (+CI): m/z for C15H19ClN2O: expected 278.1. found 279.2 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washThe combined organic phase was washed with saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash column chromatography (silica gel, 0-25% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-21d53fef447844f2b918e4320bf52abe
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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