Methanol → Methyl 7-chlorothieno[3,2-B]pyridine-2-carboxylate

HRID 2407213Notes

Reaction equation

HRID 2407213 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[CH:9][S:10][C:3]=12.C([Li])CCC.Cl[C:17]([O:19][CH3:20])=[O:18].CO>C1COCC1.ClCCl.CCCCCC.C(OCC)C>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:17]([O:19][CH3:20])=[O:18])[S:10][C:3]=12

Participants

8

Reactant 4

HCID 887MethanolHCID 6586Methyl chloroformateHCID 112752517-Chlorothieno[3,2-b]pyridineHCID 178418339Butyllithium

Product 1

HCID 59424429Methyl 7-chlorothieno[3,2-B]pyridine-2-carboxylate

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 21584099Diethylether hexaneSolvent

Procedure

7-chlorothieno[3,2-b]pyridine (19.7 g, 0.116 mol) was taken up in THF (400 mL) and cooled to approximately −70 C. The n-butyllithium (1.6M, 80 mL, 0.128 mol) was added dropwise with stirring under an atmosphere of nitrogen. The solution was stirred at −70 C for 1 hour at which time neat methyl chloroformate was added via dropwise addition. The reaction mixture gradually warmed to room temperature and was stirred for over the weekend. The reaction mixture was treated with 25 mL of methanol and then concentrated to dryness leaving a maroon residue. The crude solid was taken up in dichloromethane and passed through a silica gel column eluting with 1:1 hexane/ethyl acetate. Fractions containing the product were combined and concentrated to give a red solid. Trituration with 9:1 hexane/diethyl ether afforded methyl 7-chlorothieno[3,2-b]pyridine-2-carboxylate as a pink solid after filtration. Yield: 14.5 g (55%); MS [M+H]+227.9; 1HNMR (CDCl3) δ: 8.7 (d, 1H), 8.3 (s, 1H), 7.4 (d, 1H) ppm.

Workup

  1. temperaturecooled to approximately −70 C
  2. additionwas added via dropwise addition
  3. stirringwas stirred for over the weekend
  4. concentrationconcentrated to dryness
  5. customleaving a maroon residue
  6. washeluting with 1:1 hexane/ethyl acetate
  7. additionFractions containing the product
  8. concentrationconcentrated
  9. customto give a red solid

Sources & evidence

ORD record
ord-726ea7a102bf4082827fbee310efd497
Source dataset
uspto-grants-2014_08
Patent number
US08809534B2

Reaction notes

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