1,3-Dichloropropane → 1-(2-Fluorophenyl)cyclobutane-1-carbonitrile

HRID 736975Notes

Reaction equation

HRID 736975 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][C:11]#[N:12].Cl[CH2:14][CH2:15][CH2:16]Cl>CS(C)=O>[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1([C:11]#[N:12])[CH2:16][CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 88811,3-DichloropropaneHCID 24758Sodium hydrideHCID 67592Benzeneacetonitrile, 2-fluoro-

Product 1

HCID 227221411-(2-Fluorophenyl)cyclobutane-1-carbonitrileYield 80.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

Slowly add NaH (922 mg, 23.0 mmol) to a solution of (2-fluorophenyl)-acetonitrile (1.27 mL, 9.95 mmol) in DMSO (40.0 mL). Stir the mixture at RT for 30 mins then add via cannula a solution of 1,3-dichloropropane (0.95 mL, 10.0 mmol) in DMSO (20 mL). After addition is complete stir at 75° C. for 5 h. Pour mixture over ice (60 g) and extract with Et2O (3×50 mL). Combine the organic solutions and wash with brine (50 mL), dry filter and concentrate. Purify the material by flash chromatography (using a linear gradient of 100% hexanes to 35% EtOAc/hexanes) to give the title compound (1.4 g, 80%) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.32 (m, 1H), 7.25 (dt, 1H, J=1.9, 8.0), 7.16 (dt, 1H, J=0.9, 7.5), 7.09 (ddd, 1H, J=1.2, 8.1, 10.7), 2.86 (m, 2H), 2.69 (m, 2H), 2.50 (m, 1H), 2.05 (m, 1H).

Workup

  1. additionAfter addition
  2. stirringis complete stir at 75° C. for 5 h
  3. extractionextract with Et2O (3×50 mL)
  4. washCombine the organic solutions and wash with brine (50 mL)
  5. customdry
  6. filtrationfilter
  7. concentrationconcentrate
  8. customPurify the material by flash chromatography (

Sources & evidence

ORD record
ord-7494a2797f364f549512a54167faddd5
Source dataset
uspto-grants-2009_09
Patent number
US07595339B2

Reaction notes

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