Dimethylformamide → HCID 58316836, compound

HRID 1187299Notes

Reaction equation

HRID 1187299 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[NH:21][S:22]([C:25]1[CH:30]=[CH:29][C:28]([CH2:31][CH3:32])=[CH:27][CH:26]=1)(=[O:24])=[O:23].CN(C)[CH:35]=[O:36]>O1CCCC1>[F:13][C:14]1[C:19]([CH:35]=[O:36])=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[NH:21][S:22]([C:25]1[CH:30]=[CH:29][C:28]([CH2:31][CH3:32])=[CH:27][CH:26]=1)(=[O:24])=[O:23]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 6468856HCID 6468856, compoundHCID 178418339Butyllithium

Product 1

HCID 58316836HCID 58316836, compoundYield 55.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To N,N-diisopropylamine (4.50 mL, 32.1 mmol) in 130 mL of tetrahydrofuran, n-butyllithium (12.8 mL, 2.50 M in hexane, 32.1 mmol) is added at −78° C. under nitrogen. After 15 minutes, N-(2,4-difluoro-phenyl)-4-ethyl-benzenesulfonamide (60, 4.344 g, 14.61 mmol) in 20 mL of tetrahydrofuran is added at −78° C. under nitrogen. After 30 minutes, N,N-dimethylformamide (2.83 mL, 36.5 mmol) is added and the reaction continued at −78° C. under nitrogen for 1 hour, then warmed to room temperature over 60 minutes. The reaction is quenched with 6 mL of 6 N aqueous hydrochloric acid. The aqueous layer is extracted with ethyl acetate. The organic layers are combined and washed with brine, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography eluting with a gradient of 5-35% ethyl acetate in hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (61, 2.634 g). MS (ESI) [M−H+]−=324.2.

Workup

  1. waitAfter 30 minutes
  2. waitthe reaction continued at −78° C. under nitrogen for 1 hour
  3. customThe reaction is quenched with 6 mL of 6 N aqueous hydrochloric acid
  4. extractionThe aqueous layer is extracted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated under vacuum
  9. customThe resulting material is purified by silica gel column chromatography
  10. washeluting with a gradient of 5-35% ethyl acetate in hexane
  11. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-7990002c58664e43af9e8b450dcb717b
Source dataset
uspto-grants-2014_03
Patent number
US08673928B2

Reaction notes

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