Dimethylformamide → HCID 18630313, compound

HRID 378049Notes

Reaction equation

HRID 378049 reaction equation
C([N:3]([CH:18](OC)[C:19](C)(C)C)[C:4](=[O:17])[C:5]1[C:10]([Si:11]([CH3:14])([CH3:13])[CH3:12])=[CH:9][C:8](Br)=[CH:7][C:6]=1[Cl:16])C.[C:25](=O)=[O:26].CC(C)=O.[Li]CCCC.CN(C=O)C.C([O-])(O)=O.[Na+]>C1COCC1>[Cl:16][C:6]1[CH:7]=[C:8]([CH:25]=[O:26])[CH:9]=[C:10]([Si:11]([CH3:12])([CH3:13])[CH3:14])[C:5]=1[C:4]([NH:3][CH2:18][CH3:19])=[O:17]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 18522661Acetone cardiceHCID 18630056HCID 18630056, compoundHCID 178418339Butyllithium

Product 1

HCID 18630313HCID 18630313, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of N-ethyl-N-(1-methoxy-2,2-dimethylpropyl)-2-chloro-4-bromo-6-(trimethylsilyl)benzamide (820 mg, 1.89 mmol) in THF (2 mL) was added dropwise to a dry-ice/acetone cooled solution of 2.5M n-BuLi in hexanes (1 mL, 2.5 mmol) in THF (2 mL). The resulting red solution was stirred at -78° C. for 15 min, then DMF (500 mL, 6.5 mmol) was added in a single portion. After 5 min, the reaction was poured into sat aq NaHCO3 and extracted with ether (2×). The combined organic extracts were dried (MgSO4) and concentrated, then a solution of this protected amide in acetone (5 mL) was charged with 6N HCl and stirred overnight at RT. The resulting mixture was poured into sat aq NaHCO3 and extracted with ether (2×), then the combined organic extracts were dried (MgSO4), concentrated, and purified by RC with 3:7 EtOAc/hexanes to give 220 mg of the title compound as a white solid, a 40% yield. m.p. 95-97° C.

Workup

  1. waitAfter 5 min
  2. additionthe reaction was poured
  3. extractionextracted with ether (2×)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. concentrationconcentrated
  6. additiona solution of this protected amide in acetone (5 mL) was charged with 6N HCl
  7. stirringstirred overnight at RT
  8. additionThe resulting mixture was poured
  9. extractionextracted with ether (2×)
  10. dry with materialthe combined organic extracts were dried (MgSO4)
  11. concentrationconcentrated
  12. custompurified by RC with 3:7 EtOAc/hexanes

Sources & evidence

ORD record
ord-0b1504ef68814b558bf0ef4f5d03e682
Source dataset
uspto-grants-2000_02
Patent number
US06028101

Reaction notes

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