Pyridine → Isopropyl 4-bromo-5-methylthiophene-2-carboxylate

HRID 2298632Notes

Reaction equation

HRID 2298632 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]([OH:10])=[O:9])[S:5][C:6]=1[CH3:7].C(Cl)(=O)C(Cl)=O.N1C=C[CH:20]=[CH:19][CH:18]=1.C(O)(C)C>ClCCl.CN(C)C=O>[Br:1][C:2]1[CH:3]=[C:4]([C:8]([O:10][CH:19]([CH3:20])[CH3:18])=[O:9])[S:5][C:6]=1[CH3:7]

Participants

7

Reactant 4

HCID 1049PyridineHCID 3776IsopropanolHCID 65578Oxalyl chlorideHCID 8188894-Bromo-5-methylthiophene-2-carboxylic acid

Product 1

HCID 18537375Isopropyl 4-bromo-5-methylthiophene-2-carboxylateYield 32.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 5 g (22.6 mmol) of 4-bromo-5-methylthiophene-2-carboxylic acid was dissolved in dry dichloromethane (200 mL) and reacted with oxalyl chloride (2 mL, 22.6 mmol) and dimethylformamide (100 μL) stirring on an ice bath for 30 min and then at room temperature for 2.5 h. The solvents were removed in vacuo and the residue was passed through silica gel, eluting off with hexanes:ethyl acetate 7/3 (v:v), ethyl acetate, and dichloromethane. The solvents were removed in vacuo and the resulting oil dissolved in dry dichloromethane (100 mL). This solution was reacted with dry pyridine (9 mL, 113 mmol) and dry isopropanol (40 mL, 522 mmol) for 88 h. The solvents were removed in vacuo and the residue partitioned between sodium bicarbonate (150 mL) and dichloromethane (75 mL). The aqueous layers were extracted with dichloromethane (2×20 mL), and the combined organic layers were washed with sodium bicarbonate (30 mL), brine (30 mL), and dried over anhydrous sodium sulfate. The solvents were removed in vacuo. The residue was purified by column chromatography eluting with hexanes:ethyl acetate 9/1 (v:v) to give isopropyl 4-bromo-5-methylthiophene-2-carboxylate (1.91 g, 32%) as a pale yellow oil. 1H-NMR NMR (DMSO-d6; 300 MHz) δ7.66 (s, 1H), 5.07 (septet, 1H, J=6.2 Hz), 2.42 (s, 3H), 1.29 (d, 6H, J=6.2 Hz). Mass spectrum (ESI, m/z): Calcd. for C9H11O2SBr 264.2 (M+H), found 264.8.

Workup

  1. waitat room temperature for 2.5 h
  2. customThe solvents were removed in vacuo
  3. washeluting off with hexanes
  4. customThe solvents were removed in vacuo
  5. dissolutionthe resulting oil dissolved in dry dichloromethane (100 mL)
  6. customThe solvents were removed in vacuo
  7. customthe residue partitioned between sodium bicarbonate (150 mL) and dichloromethane (75 mL)
  8. extractionThe aqueous layers were extracted with dichloromethane (2×20 mL)
  9. washthe combined organic layers were washed with sodium bicarbonate (30 mL), brine (30 mL)
  10. dry with materialdried over anhydrous sodium sulfate
  11. customThe solvents were removed in vacuo
  12. customThe residue was purified by column chromatography
  13. washeluting with hexanes

Sources & evidence

ORD record
ord-bd576fdefe454206b4af569a253daadb
Source dataset
uspto-grants-2002_12
Patent number
US06492403B1

Reaction notes

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