Hydrochloric Acid → 5-(Azetidin-1-ylcarbonyl)-2,3-dichloropyridine

HRID 600545ノート

反応式

HRID 600545 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([OH:11])=O)[CH:5]=[N:6][C:7]=1[Cl:8].Cl.CCOCC.C(Cl)(=O)C(Cl)=O.Cl.[NH:25]1[CH2:28][CH2:27][CH2:26]1.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[N:25]1([C:9]([C:4]2[CH:5]=[N:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)=[O:11])[CH2:28][CH2:27][CH2:26]1

参加物

9

反応物 6

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 2479875,6-Dichloronicotinic acidHCID 12308726Azetidine hydrochloride

生成物 1

HCID 536296165-(Azetidin-1-ylcarbonyl)-2,3-dichloropyridine収率 47%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒

実験手順

5,6-Dichloropyridine-3-carboxylic acid (CAS no. 41667-95-2) (32 g, 0.17 mol) was suspended in DCM (500 mL) and 1M HCl in ether (0.17 L, 0.17 mol) added. Oxalyl chloride (17 mL, 0.20 mol) and then DMF (2 drops) were added and stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure, azeotroped with toluene and re-dissolved into DCM (250 mL). Azetidine hydrochloride (17.5 g, 0.18 mol) was added, followed by triethylamine (51 mL, 0.37 mol) and the reaction stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure then water (500 mL) and ethyl acetate (500 mL) were added. The organic layer was separated and the aqueous phase was re-extracted with ethyl acetate (5×150 mL). The combined organics were washed with citric acid (250 mL), saturated sodium bicarbonate solution (250 mL), brine (250 mL), dried (MgSO4), filtered and evaporated under reduced pressure to give a solid which was recrystallised in ethyl acetate and dried under reduced pressure to give the product (18.2 g, 47%). 1H NMR δ (400 MHz, CDCl3) 2.34 (quintet, 2H), 4.20 (s, 2H), 4.27 (s, 2H), 8.02 (d, 1H), 8.44 (d, 1H); m/z 231 (M+H)+.

後処理

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customazeotroped with toluene
  3. dissolutionre-dissolved into DCM (250 mL)
  4. stirringthe reaction stirred at room temperature for 2 hours
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. additionwater (500 mL) and ethyl acetate (500 mL) were added
  7. customThe organic layer was separated
  8. extractionthe aqueous phase was re-extracted with ethyl acetate (5×150 mL)
  9. washThe combined organics were washed with citric acid (250 mL), saturated sodium bicarbonate solution (250 mL), brine (250 mL)
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. customevaporated under reduced pressure
  13. customto give a solid which
  14. customwas recrystallised in ethyl acetate
  15. customdried under reduced pressure

出典と根拠

ORDレコード
ord-c204bb51455549d58a5ef16f4ba94626
出典データセット
uspto-grants-2011_03
特許番号
US07902200B2

反応ノート

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