Dimethylformamide → HCID 59006374, compound

HRID 2378984Notes

Reaction equation

HRID 2378984 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([NH:6][C:7](=[O:12])[C:8]([CH3:11])([CH3:10])[CH3:9])=[CH:2]1.[Li]CCCC.CN([CH:21]=[O:22])C>C1COCC1>[CH:21]([C:2]1[S:1][CH:5]=[CH:4][C:3]=1[NH:6][C:7](=[O:12])[C:8]([CH3:9])([CH3:11])[CH3:10])=[O:22]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 12717062HCID 12717062, compoundHCID 178418339Butyllithium

Product 1

HCID 59006374HCID 59006374, compoundYield 80.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To an oven dried flask was charged with N-(thiophen-3-yl)pivalamide (2.0 g, 10.91 mmol) and THF (50 mL) at rt, then the light tan solution was cooled down to −78° C., followed by dropwise addition of n-BuLi (2.4M in hexanes, 9.60 mL, 24.01 mmol) over 5 min under N2. The resulting off-white suspension was stirred for 1 hr, followed by addition of DMF (3.21 mL, 41.5 mmol) through a syringe over 2 min. In 20 min, the suspension became tan solution and the reaction mixture was warmed to rt and continued stirring for 30 min. The conversion was completed as determined by TLC, thus the reaction was quenched with sat. NH4Cl, partitioned between Et2O/H2O (150 mL/50 mL), after separation, the organic solution was washed with brine, dried (Na2SO4), concentrated and purified on Biotage Fresh Collector eluting with 10˜40% EtOAc/Hexanes to afford the expected product, N-(2-formylthiophen-3-yl)pivalamide (1.85 g, 80%) as a tan oil. 1H-NMR (500 MHz, CHLOROFORM-D) δ ppm 1.32 (s, 9 H) 7.68 (d, J=5.19 Hz, 1 H) 8.19 (d, J=5.19 Hz, 1 H) 9.71 (s, 1 H) 10.97 (s, 1 H); Mass spec. 212.09 (MH+) calc. for C10H13NO2S 211.07.

Workup

  1. customTo an oven dried flask
  2. waitIn 20 min
  3. temperaturethe reaction mixture was warmed to rt
  4. stirringcontinued stirring for 30 min
  5. customthus the reaction was quenched with sat. NH4Cl
  6. custompartitioned between Et2O/H2O (150 mL/50 mL)
  7. customafter separation
  8. washthe organic solution was washed with brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. custompurified on Biotage Fresh Collector
  12. washeluting with 10˜40% EtOAc/Hexanes

Sources & evidence

ORD record
ord-3526bb73bc434ab0bb3affdd3cc59240
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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