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

HRID 525794Notes

Reaction equation

HRID 525794 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-490aefdf1bd7416cb353719fc94ba182
Source dataset
uspto-grants-2016_05
Patent number
US09340555B2

Reaction notes

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