Sodium Chloride → 7-Chloro-4-(3-fluoro-benzyl)-5-oxo-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester

HRID 902494Notes

Reaction equation

HRID 902494 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:11](=[O:12])[N:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)[C:9]2[CH:21]=[CH:22][S:23][C:8]=2[C:7]=1O)=[O:5])[CH3:2].C(Cl)(=O)C([Cl:28])=O.[Na+].[Cl-]>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:11](=[O:12])[N:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)[C:9]2[CH:21]=[CH:22][S:23][C:8]=2[C:7]=1[Cl:28])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 5234Sodium ChlorideHCID 65578Oxalyl chlorideHCID 693160674-(3-Fluoro-benzyl)-7-hydroxy-5-oxo-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester

Product 1

HCID 693126547-Chloro-4-(3-fluoro-benzyl)-5-oxo-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl esterYield 88.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-30 °C

Procedure

4-(3-Fluoro-benzyl)-7-hydroxy-5-oxo-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester (15) (60 g, 0.17 mol) was dissolved in 600 mL anhydrous DMF under a blanket of argon and cooled to −30° C. Oxalyl chloride (40.7 mL, 0.47 mol) was then added very slowly (producing a large volume of gas), with the reaction vessel open to the atmosphere. The solution was then heated to 75° C. for 2 hours. The solution was cooled to room temperature and poured into a solution of 150 g. NaCl in 6 L ice water without stirring. The mixture was allowed to sit without stirring for 15 minutes, and was then stirred vigorously for 1 minute with a spatula. The precipitated solid product was collected by vacuum filtration to yield 55 g (87% yield) of 7-chloro-4-(3-fluoro-benzyl)-5-oxo-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester. 1H-NMR (DMSO-d6) δ 1.30 (t, J=7.2 Hz, 3H), 4.34 (q, J=7.2 Hz, 2H), 5.45 (s, 2H), 7.06-7.17 (m, 3H), 7.37 (m, 1H), 7.49 (d, J=5.6 Hz, 1H), 8.20 (d, J=5.6 Hz, 1H) ppm; EIMS m/z 366 (M+1).

Workup

  1. customproducing a large volume of gas), with the reaction vessel open to the atmosphere
  2. temperatureThe solution was then heated to 75° C. for 2 hours
  3. temperatureThe solution was cooled to room temperature
  4. additionpoured into a solution of 150 g
  5. stirringwas then stirred vigorously for 1 minute with a spatula
  6. filtrationThe precipitated solid product was collected by vacuum filtration

Sources & evidence

ORD record
ord-cc52c079417a4ee6af0f6e6b95ebddc5
Source dataset
uspto-grants-2008_04
Patent number
US07365200B2

Reaction notes

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