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

HRID 1261199Notes

Reaction equation

HRID 1261199 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.[Li]CCCC.Cl[C:17]([O:19][CH3:20])=[O:18]>C1COCC1>[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

5

Reactant 3

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

Product 1

HCID 59424429Methyl 7-chlorothieno[3,2-B]pyridine-2-carboxylateYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2 (7.0 g, 41.3 mmol) in anhydrous THF (100 mL) at −78° C. under a nitrogen atmosphere was added n-BuLi (24.7 mL, 2.5 M in hexanes, 61.8 mmol). After 1 hour, methyl chloroformate (9.6 ml, 124 mmol) was added and the reaction mixture was stirred for an extra hour at the same temperature, quenched with excess methanol and allowed to warm to room temperature. The solvent was then evaporated and the residue was purified by flash chromatography using hexane—AcOEt (70:30) as an eluent. The product from the column was re-crystallized from ethyl acetate to afford title compound 37 (4.3 g, 46% yield) as a white solid 1H NMR (400 MHz, DMSO-d6) δ(ppm): 8.75 (dd, J=0.8 and 4.8 Hz, 1H), 8.26 (d, J=0.8 Hz, 1H), 7.74 (dd, J=0.8 and 5.2 Hz, 1H), 3.93 (s, 3H).

Workup

  1. customquenched with excess methanol
  2. customThe solvent was then evaporated
  3. customthe residue was purified by flash chromatography
  4. customThe product from the column was re-crystallized from ethyl acetate

Sources & evidence

ORD record
ord-01c71f1a44e94ad680d3665f0319d55c
Source dataset
uspto-grants-2013_06
Patent number
US08470850B2

Reaction notes

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