Dimethylcarbamoyl Chloride → HCID 90203294, compound

HRID 1480341Notes

Reaction equation

HRID 1480341 reaction equation
[CH:1]1([C:4]2[CH:5]=[N:6][CH:7]=[CH:8][C:9]=2[O:10][CH:11]([CH3:14])[CH2:12][F:13])[CH2:3][CH2:2]1.[N+:15]1([O-])C=CC=C[CH:16]=1.CN(C)C(Cl)=O.C[Si](C#N)(C)C>ClCCl>[CH:1]1([C:4]2[C:9]([O:10][CH:11]([CH3:14])[CH2:12][F:13])=[CH:8][C:7]([C:16]#[N:15])=[N:6][CH:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 6598Dimethylcarbamoyl ChlorideHCID 12753Pyridine N-OxideHCID 82115Trimethylsilyl cyanideHCID 90204041HCID 90204041, compound

Product 1

HCID 90203294HCID 90203294, compoundYield 21.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 3-cyclopropyl-4-(2-fluoro-1-methyl-ethoxy)pyridine (example 287b, 6.26 g, 32.1 mmole) in dichloromethane (100 mL) was added m-cpba 77% (10.8 g, 48.1 mmole) and the reaction was stirred at room temperature for 16 hours. Reaction mixture was diluted with dichloromethane and extracted with a 1M aqueous solution of sodium bicarbonate. Organic phase was collected and the aqueous phase was back-extracted with dichloromethane. Combined organic phases were dried over magnesium sulfate and evaporated down to dryness. The crude pyridine-oxide intermediate (6.97 g) was used without any purification. To a solution of the crude pyridine-oxide (6.97 g, 33.0 mmole) in dichloromethane (110 mL) was added dimethylcarbamoylchloride (CAN 79-44-7, 5.32 g, 4.55 mL, 49.5 mmole) and trimethylsilylcyanide (8.18 g, 10.3 mL, 82.5 mmole). The reaction mixture was stirred at room temperature for 16 hours and the reaction was quenched by addition of a 1M aqueous solution of sodium bicarbonate. The bi-phasic mixture was vigorously stirred for 10 minutes and then poured into a separatory funnel. The organic phase was extracted and collected. The aqueous phase was back-extracted with dichloromethane. Combined organic phases were dried over magnesium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a gradient of heptane and ethyl acetate to yield the title compound (1.5 g, 21%). MS (ESI, m/z): 221.6 (M+H+).

Workup

  1. customReaction mixture
  2. extractionextracted with a 1M aqueous solution of sodium bicarbonate
  3. customOrganic phase was collected
  4. extractionthe aqueous phase was back-extracted with dichloromethane
  5. dry with materialCombined organic phases were dried over magnesium sulfate
  6. customevaporated down to dryness
  7. customThe crude pyridine-oxide intermediate (6.97 g) was used without any purification
  8. stirringThe reaction mixture was stirred at room temperature for 16 hours
  9. customthe reaction was quenched by addition of a 1M aqueous solution of sodium bicarbonate
  10. stirringThe bi-phasic mixture was vigorously stirred for 10 minutes
  11. additionpoured into a separatory funnel
  12. extractionThe organic phase was extracted
  13. customcollected
  14. extractionThe aqueous phase was back-extracted with dichloromethane
  15. dry with materialCombined organic phases were dried over magnesium sulfate
  16. customevaporated down to dryness
  17. customThe crude material was purified by flash chromatography on silica eluting with a gradient of heptane and ethyl acetate

Sources & evidence

ORD record
ord-dc8c79556a27481eb139343982f12bcc
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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