4-Fluorobenzaldehyde → HCID 60204545, compound

HRID 2267411Notes

Reaction equation

HRID 2267411 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([CH2:6][CH2:7][N:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:2]1.C([Li])CCC.[F:18][C:19]1[CH:26]=[CH:25][C:22]([CH:23]=[O:24])=[CH:21][CH:20]=1>C1COCC1.C([O-])(O)=O.[Na+].CCOC(C)=O>[F:18][C:19]1[CH:26]=[CH:25][C:22]([CH:23]([C:2]2[S:1][CH:5]=[CH:4][C:3]=2[CH2:6][CH2:7][N:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)[OH:24])=[CH:21][CH:20]=1

Participants

7

Reactant 3

HCID 680234-FluorobenzaldehydeHCID 57428857HCID 57428857, compoundHCID 178418339Butyllithium

Product 1

HCID 60204545HCID 60204545, compoundYield 21.1%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 1-(2-(thiophen-3-yl)ethyl)pyrrolidine (1.0 g, 5.5 mmol) in THF (11.0 mL) was cooled to −78° C. in a dry-ice acetone bath before dropwise addition of n-butyllithium solution (2.5 M in hexanes, 2.4 mL, 6.0 mmol). The reaction mixture was stirred at −78° C. for 1 h and then neat p-fluorobenzaldehyde (0.65 mL, 6.1 mmol) was added dropwise via syringe. The mixture was allowed to warm to room temperature over 16 h and subsequently diluted with saturated aqueous NaHCO3 and EtOAc. The organic layer was separated, washed with brine, and dried over Na2SO4. The residue remaining after solvent removal in vacuo was purified by flash chromatography to afford the desired alkylation product as a white solid (353 mg, 1.16 mmol, 21% yield). MS (M+H)+ 306.

Workup

  1. temperatureto warm to room temperature over 16 h
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. customafter solvent removal in vacuo
  6. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-560873c70bf84214a9db8d975bd8c946
Source dataset
uspto-grants-2010_12
Patent number
US07858785B2

Reaction notes

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