Triethylamine → 5-Fluoro-2-methoxy-4-oxiran-2-ylbenzonitrile

HRID 1186987Notes

Reaction equation

HRID 1186987 reaction equation
[F:1][C:2]1[C:3]([CH2:12][CH2:13][OH:14])=[CH:4][C:5]([O:10][CH3:11])=[C:6]([CH:9]=1)[C:7]#[N:8].CCN(CC)CC.CS(Cl)(=O)=O.[Cl-].[NH4+].C1CCN2C(=NCCC2)CC1.ClC1C=CC=C(C(OO)=O)C=1>ClCCl.O.C(=O)(O)[O-].[Na+]>[F:1][C:2]1[C:3]([CH:12]2[CH2:13][O:14]2)=[CH:4][C:5]([O:10][CH3:11])=[C:6]([CH:9]=1)[C:7]#[N:8]

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chlorideHCID 70297m-Chloroperbenzoic acidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 666439605-Fluoro-4-(2-hydroxyethyl)-2-methoxybenzonitrile

Product 1

HCID 866473025-Fluoro-2-methoxy-4-oxiran-2-ylbenzonitrile

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 5-fluoro-4-(2-hydroxyethyl)-2-methoxybenzonitrile (0.68 g, 3.5 mmol) and Et3N (0.82 mL, 5.9 mmol) in dichloromethane (5 mL) was added methanesulfonyl chloride (0.33 mL, 4.2 mmol) at 0° C. After 15 min. the reaction mixture was poured into saturated ammonium chloride and extracted with dichloromethane. The combined organics were washed with 1 N HCl, saturated sodium bicarbonate solution, and brine, then dried (MgSO4) and concentrated in vacuo. The residue was re-dissolved in dichloromethane (5 mL), treated with DBU (0.79 mL, 5.2 mmol) and stirred for 2 h. TLC monitoring showed conversion to the olefin. The reaction mixture was diluted with water and extracted with dichloromethane. The combined organics were washed with 1 N HCl, saturated sodium bicarbonate solution, and brine, then dried (MgSO4) and concentrated in vacuo. The resulting olefin was dissolved in dichloromethane (5 mL) and treated with meta-chloro perbenzoic acid (0.72 g, 4.2 mmol) at 0° C. After 3 h, the mixture was diluted with saturated sodium bicarbonate solution and extracted with dichloromethane (twice). The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude epoxide was purified by silica gel column chromatography (5→80% EtOAc:hexane) to provide 5-fluoro-2-methoxy-4-oxiran-2-ylbenzonitrile. 1H NMR (500 MHz, CD3OD) δ 7.32 (d, J=5.3 Hz, 1H), 6.82 (d, J=5.4 Hz, 1H), 4.19 (m, 1H), 3.96 (s, 3H), 3.27 (m, 1H), 2.76 (m, 1H);

Workup

  1. extractionextracted with dichloromethane
  2. washThe combined organics were washed with 1 N HCl, saturated sodium bicarbonate solution, and brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was re-dissolved in dichloromethane (5 mL)
  6. extractionextracted with dichloromethane
  7. washThe combined organics were washed with 1 N HCl, saturated sodium bicarbonate solution, and brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. dissolutionThe resulting olefin was dissolved in dichloromethane (5 mL)
  11. waitAfter 3 h
  12. extractionextracted with dichloromethane (twice)
  13. washThe combined organic extracts were washed with brine
  14. dry with materialdried (MgSO4)
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. customThe crude epoxide was purified by silica gel column chromatography (5→80% EtOAc:hexane)

Sources & evidence

ORD record
ord-634e6ed6735b440e96d5d7390160846a
Source dataset
uspto-grants-2014_03
Patent number
US08673920B2

Reaction notes

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