Piperidine → 4-Bromo-2-(pyrrolidin-1-yl)benzaldehyde

HRID 2278208Notes

Reaction equation

HRID 2278208 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[C:4](F)[CH:3]=1.[NH:11]1[CH2:16][CH2:15][CH2:14][CH2:13]C1.CC(N(C)C)=O>CCOC(C)=O>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([N:11]2[CH2:13][CH2:14][CH2:15][CH2:16]2)[CH:3]=1

Participants

5

Reactant 3

HCID 8082PiperidineHCID 31374DimethylacetamideHCID 1435174-Bromo-2-fluorobenzaldehyde

Product 1

HCID 431739434-Bromo-2-(pyrrolidin-1-yl)benzaldehydeYield 96,679.602%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A 20 mL screwtop vial was charged with 4-bromo-2-fluorobenzaldehyde (200 mg, 0.985 mmol), piperadine (116 μL, 1.19 mmol), and DMA (1 mL). The reaction was heated to 120° C. for 3 h. The reaction was diluted in EtOAc and extracted with brine (3×). The organics were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was chromatographed on a silica gel column (0% to 20% EtOAc in hexanes) and yielded 4-bromo-2-(pyrrolidin-1-yl)benzaldehyde (242 g, 92%). 1H NMR 400 MHz (CDCl3) δ 10.21 (s, 1H), 7.66 (dd, J=8.3, 2.4 Hz, 1H), 7.31-7.17 (m, 2H), 4 (m, 4H), 1.78 (m, 4H), 1.71-1.60 (m, 2H). LCMS (ESI, m/z): 268 [M+H]+.

Workup

  1. extractionextracted with brine (3×)
  2. dry with materialThe organics were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was chromatographed on a silica gel column (0% to 20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9d932f02a8584de1a928545209c1d8a6
Source dataset
uspto-grants-2015_09
Patent number
US09133148B2

Reaction notes

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