Thionyl Chloride → (7-Chlorothieno[3,2-b]pyridin-2-yl)methanol

HRID 1825204Notes

Reaction equation

HRID 1825204 reaction equation
[Li+].[Cl:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]2[CH:9]=[C:10]([C:12]([O-])=[O:13])[S:11][C:4]=12.S(Cl)(Cl)=O.[BH4-].[Na+]>CN(C=O)C.C(Cl)(Cl)Cl>[OH:13][CH2:12][C:10]1[S:11][C:4]2[C:5](=[N:6][CH:7]=[CH:8][C:3]=2[Cl:2])[CH:9]=1

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 4311764Sodium borohydrideHCID 23677819Lithium 7-chlorothieno[3,2-b]pyridine-2-carboxylate

Product 1

HCID 22143534(7-Chlorothieno[3,2-b]pyridin-2-yl)methanolYield 40%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent2×

Procedure

7-Chloro-thieno[3,2-b]pyridine-2-carboxylic acid lithium salt (2.0 g, 9.1 mmole) was dissolved in a solution of DMF (10 mL) and chloroform (50 mL). The carboxylate was treated with thionyl chloride (2.0 mL, 27.3 mmole) and refluxed for one hour. The resultant acid chloride was cooled to room temperature and added dropwise to a solution of sodium borohydride (0.7 g, 18.2 mmole) in DMF (10 mL) at 0° C. The temperature was allowed to reach room temperature over 2 hours and the reaction was quenched with concentrated HCl. The reaction mixture was neutralized with NaOH and the workup was performed with MTBE, brine and MgSO4. The crude product was triturated with MTBE, which provided the title compound as a beige solid (0.7 g, 40%): 1H-NMR (DMSO-d6, 400 MHz) δ 8.58 (1H, d, J=5.1 Hz), 7.51 (1H, d, J=5.1 Hz), 7.47 (1H, s), 5.94 (1H, t, J=5.8 Hz), 4.84–4.82 (2H, m); MS m/z 200 (M+H)+.

Workup

  1. temperaturerefluxed for one hour
  2. customthe reaction was quenched with concentrated HCl
  3. customThe crude product was triturated with MTBE, which

Sources & evidence

ORD record
ord-b63f11c2268c4aa9b535e18a97a37eb1
Source dataset
uspto-grants-2006_05
Patent number
US07045528B2

Reaction notes

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