Dimethylformamide → HCID 86677872, compound

HRID 1499955Notes

Reaction equation

HRID 1499955 reaction equation
[Cl:1][C:2]1[C:3]([F:20])=[C:4]([CH:14]2[CH2:18][NH:17][C:16](=[O:19])[CH2:15]2)[C:5]([O:11][CH2:12][CH3:13])=[C:6]([CH:8](O)[CH3:9])[CH:7]=1.CN(C)C=O.S(Cl)([Cl:28])=O>C(Cl)Cl>[Cl:1][C:2]1[C:3]([F:20])=[C:4]([CH:14]2[CH2:18][NH:17][C:16](=[O:19])[CH2:15]2)[C:5]([O:11][CH2:12][CH3:13])=[C:6]([CH:8]([Cl:28])[CH3:9])[CH:7]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 86677873HCID 86677873, compound

Product 1

HCID 86677872HCID 86677872, compoundYield 84.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

The mixture of diastereoisomers from step 6 were each processed individually to the final products. A solution of 4-[3-chloro-6-ethoxy-2-fluoro-5-(1-hydroxyethyl)phenyl]pyrrolidin-2-one (0.41 g, 1.4 mmol) (from Step 6) in methylene chloride (12 mL) was treated with N,N-dimethylformamide (0.011 mL, 0.14 mmol) followed by thionyl chloride (0.21 mL, 2.9 mmol) dropwise and stirred at 20° C. for 30 min. The reaction mixture was added dropwise to ice cooled saturated sodium bicarbonate solution and extracted with dichloromethane. The organic layer was separated and washed with brine, dried over sodium sulfate, filtered, and concentrated to give the desired products [from peak 1 (0.38 g, 87%); from peak 2 (0.39 g, 89%)] along with 17-18% of the styrene that formed from chloride elimination. These mixtures were used without further purification. From peak 1: LCMS for C14H17Cl2FNO2 (M+H)+: m/z=320.1; Found: 320.0. From peak 2: LCMS for C14H17Cl2FNO2 (M+H)+: m/z=320.1; Found: 320.0.

Workup

  1. additionThe mixture of diastereoisomers from step 6
  2. additionThe reaction mixture was added dropwise to ice cooled saturated sodium bicarbonate solution
  3. extractionextracted with dichloromethane
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-7d8f3c2a1eed43e5833f91305c2baadc
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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