Triethylamine → 1-(3-(Pyridin-4-yl)-7a-(pyrrolidin-1-yl)-3a,4,7,7a-tetrahydroisoxazolo[4,5-c]pyridin-5(6H)-yl)ethanone

HRID 2388697Notes

Reaction equation

HRID 2388697 reaction equation
[N:1]1([C:6]2[CH2:11][CH2:10][N:9]([C:12](=[O:14])[CH3:13])[CH2:8][CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH:15]/[N:16]=[C:17](\Cl)/[C:18]1[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=1.C(N(CC)CC)C>C(Cl)Cl>[N:21]1[CH:22]=[CH:23][C:18]([C:17]2[CH:7]3[CH2:8][N:9]([C:12](=[O:14])[CH3:13])[CH2:10][CH2:11][C:6]3([N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[O:15][N:16]=2)=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 141055951-(4-(Pyrrolidin-1-yl)-5,6-dihydropyridin-1(2H)-yl)ethanoneHCID 135723912N-hydroxypyridine-4-carbonimidoyl chloride

Product 1

HCID 686439771-(3-(Pyridin-4-yl)-7a-(pyrrolidin-1-yl)-3a,4,7,7a-tetrahydroisoxazolo[4,5-c]pyridin-5(6H)-yl)ethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Conditions

Temperature
0 °C

Procedure

1-(4-(Pyrrolidin-1-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone (1.2 g, 6.176 mmol) (synthesis: see below) was dissolved in methylene chloride (10 ml) and the solution was cooled to 0° C. under an inert gas. (Z)-N-Hydroxyisonicotinimidoyl chloride (1.45 g, 9.264 mmol), dissolved in methylene chloride (5 ml), and triethyl-amine (2.1 ml, 14.82 mmol), dissolved in methylene chloride (5 ml), were added, stir for 15 h, during this allow to warm to room temperature. The mixture was diluted with methylene chloride (30 ml) and washed water (20 ml) and citric acid (10%, 20 ml). The aqueous phase was neutralized with sodium bicarbonate and extracted with methylene chloride and the combined organic phases were washed with saturated sodium chloride solution, dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel) with ethyl acetate/methanol/ammonia (25% eq.) 100/10/1. The yield was 0.64 g (33%).

Workup

  1. additionwere added
  2. temperatureto warm to room temperature
  3. washwashed water (20 ml) and citric acid (10%, 20 ml)
  4. extractionextracted with methylene chloride
  5. washthe combined organic phases were washed with saturated sodium chloride solution
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by column chromatography (silica gel) with ethyl acetate/methanol/ammonia (25% eq.) 100/10/1

Sources & evidence

ORD record
ord-4f23282ce97e4e13bf21d57d10b8082e
Source dataset
uspto-grants-2012_09
Patent number
US08268814B2

Reaction notes

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