2-Chloro-6-(hydroxymethyl)-4-[2-(trimethylsilyl)ethynyl]pyridin-3-ol → [7-Chloro-2-(trimethylsilyl)furo[2,3-c]pyridin-5-yl]methanol

HRID 1072978Notes

Reaction equation

HRID 1072978 reaction equation
[Cl:1][C:2]1[C:7]([OH:8])=[C:6]([C:9]#[C:10][Si:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=[C:4]([CH2:15][OH:16])[N:3]=1>CCO>[Cl:1][C:2]1[N:3]=[C:4]([CH2:15][OH:16])[CH:5]=[C:6]2[CH:9]=[C:10]([Si:11]([CH3:12])([CH3:14])[CH3:13])[O:8][C:7]=12

Participants

3

Reactant 1

HCID 105152062-Chloro-6-(hydroxymethyl)-4-[2-(trimethylsilyl)ethynyl]pyridin-3-ol

Product 1

HCID 22047422[7-Chloro-2-(trimethylsilyl)furo[2,3-c]pyridin-5-yl]methanolYield 46%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

C3 (7.9 g, 31.2 mmol) and cuprous iodide (297 mg, 1.6 mmol) in 60 mL EtOH/60 mL TEA are added to a flask. The reaction is placed in an oil bath at 70° C. for 3.5 h, is cooled to rt, and concentrated in vacuo. The residue is partitioned between 100 mL 5% HCl and CH2Cl2 (4×50 mL). The combined organic layer is dried over MgSO4, filtered, and concentrated in vacuo to give 6.5 g of a crude amber solid. The crude material is chromatographed over 300 g silica gel (230-400 mesh) eluting with 30-40% EtOAc/hexane. Two sets of fractions with two different desired compounds are identified by TLC/UV. The two compounds eluted separately. The early-eluting pool of fractions is combined and concentrated to afford [7-chloro-2-(trimethylsilyl)furo[2,3-c]pyridin-5-yl]methanol (C5) as a white solid (46% yield). The later-eluting pool of fractions is combined and concentrated to provide (7-chlorofuro[2,3-c]pyridin-5-yl)methanol (C4) as a white solid (27% yield). MS (EI) for C8H6ClNO2, m/z: 183 (M)+ for C4. HRMS (FAB) calculated for C11H14ClNO2Si m/z: 255.0482, found 255.0481 for C5.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue is partitioned between 100 mL 5% HCl and CH2Cl2 (4×50 mL)
  3. dry with materialThe combined organic layer is dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give 6.5 g of a crude amber solid
  7. customThe crude material is chromatographed over 300 g silica gel (230-400 mesh)
  8. washeluting with 30-40% EtOAc/hexane
  9. washThe two compounds eluted separately
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-999bed4c8e86428bafe5ae301d30453c
Source dataset
uspto-grants-2005_06
Patent number
US06911543B2

Reaction notes

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