Dimethylformamide → 2-(Diethoxymethyl)furo[3,2-c]pyridine

HRID 1830537Notes

Reaction equation

HRID 1830537 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:20]([O:22][CH:23]([O:26][CH2:27][CH3:28])[CH2:24][CH3:25])[CH3:21].[NH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1.CN(C=[O:39])C>CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:20]([O:22][CH:23]([O:26][CH2:27][CH3:28])[C:24]1[O:39][C:32]2[CH:33]=[CH:34][N:29]=[CH:30][C:31]=2[CH:25]=1)[CH3:21]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8082PiperidineHCID 11776TriphenylphosphineHCID 20858Propane, 1,1-diethoxy-

Product 1

HCID 220473402-(Diethoxymethyl)furo[3,2-c]pyridineYield 64%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

Procedure

C10 (3.5 g, 15.8 mmol) is added to a suspension of triphenylphosphine (166 mg, 0.63 mmol) and palladium acetate (71 mg, 0.32 mmol) in 25 mL DMF in dry flask under N2. Propioaldehyde diethyl acetal (2.3 mL, 15.8 mmol), cuprous iodide (120 mg, 0.63 mmol), and piperidine (1.6 mL, 16 mmol), are added successively, and the reaction is stirred 6 h at rt. The mixture is diluted with 125 mL EtOAc, is extracted with 4×50 mL 50% saturated 1:1 NaCl/NaHCO3, and the organic layer is dried over anhydrous Na2SO4 and then filtered. The dried organic layer is concentrated in vacuo to a dark oil. The crude material is chromatographed over 40 g silica gel (Biotage), eluting with 50% EtOAc/hexane. The fractions with the desired compound are combined and concentrated to afford 2-(diethoxymethyl)furo[3,2-c]pyridine (C11) (64% yield). HRMS (FAB) calculated for C12H15NO3+H: 222.1130, found 222.1123 (M+H)+.

Workup

  1. extractionis extracted with 4×50 mL 50% saturated 1:1 NaCl/NaHCO3
  2. dry with materialthe organic layer is dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationThe dried organic layer is concentrated in vacuo to a dark oil
  5. customThe crude material is chromatographed over 40 g silica gel (Biotage)
  6. washeluting with 50% EtOAc/hexane
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-4855e107ab5949dca0198f5ae40687c6
Source dataset
uspto-grants-2006_06
Patent number
US07067515B2

Reaction notes

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