Nitrogen → 5-(2-Methyl-[1,3]dioxolan-2-yl)-thiophene-3-carbaldehyde

HRID 42809Notes

Reaction equation

HRID 42809 reaction equation
N#N.Br[C:4]1[CH:5]=[C:6]([C:9]2([CH3:14])[O:13][CH2:12][CH2:11][O:10]2)[S:7][CH:8]=1.[Li]CCCC.CN([CH:23]=[O:24])C>CCOCC.CCCCCC>[CH3:14][C:9]1([C:6]2[S:7][CH:8]=[C:4]([CH:23]=[O:24])[CH:5]=2)[O:13][CH2:12][CH2:11][O:10]1

Participants

7

Reactant 4

HCID 947NitrogenHCID 6228DimethylformamideHCID 12566255HCID 12566255, compoundHCID 178418339Butyllithium

Product 1

HCID 866494855-(2-Methyl-[1,3]dioxolan-2-yl)-thiophene-3-carbaldehyde

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8058HexaneSolvent

Procedure

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of 2-(4-bromo-thiophen-2-yl)-2-methyl-[1,3]dioxolane (1.00 g, 4.01 mmol) in Et2O (36.0 mL) at −78° C. was added dropwise n-BuLi (2.5 mL of a 1.6M solution in hexane, 4.00 mmol) over 15 min. The reaction mixture was then stirred at −78° C. for 15 min before DMF (3.1 mL, 40.14 mmol) was added dropwise. The cooling bath was removed and the reaction mixture was stirred for 10 min. Sat. aq. NaH4Cl (40 mL) was added and the aqueous layer was extracted with EA (2×100 mL). The combined org. extracts were dried over MgSO4, filtered, and the solvent was removed under reduced pressure to give crude 5-(2-methyl-[1,3]dioxolan-2-yl)-thiophene-3-carbaldehyde as an yellow oil. LC-MS-conditions 02: tR=0.84 min. The crude material was dissolved, under inert atmosphere (N2) in MeOH (9.98 mL) and treated at 0° C., portionwise with NaBH4 (284 mg, 7.21 mmol). The reaction mixture was stirred at rt for 2 h. The reaction mixture was poured in water (16 mL) and the aq. layer was extracted with EA (2×100 mL). The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (50:50 hept-EA) gave the title compound as a yellow oil. TLC:rf (50:50 EA-Hept)=0.21. LC-MS-conditions 02: tR=0.71 min; [M+H]+=201.49.

Workup

  1. additionwas added dropwise
  2. customThe cooling bath was removed
  3. additionSat. aq. NaH4Cl (40 mL) was added
  4. extractionthe aqueous layer was extracted with EA (2×100 mL)
  5. dry with materialextracts were dried over MgSO4
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-845aa4c0efe44563905dc62f33335212
Source dataset
uspto-grants-2013_09
Patent number
US08536209B2

Reaction notes

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