Chlorosuccinimide → HCID 89996300, compound

HRID 2276055Notes

Reaction equation

HRID 2276055 reaction equation
[OH:1][N:2]=[CH:3][C:4]1[N:9]=[CH:8][C:7]2[C:10]3([CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]3)[O:11][CH2:12][C:6]=2[CH:5]=1.C1C(=O)N(Cl)C(=O)C1.[Cl:31][C:32]1[CH:37]=[C:36]([C:38]([C:40]([F:43])([F:42])[F:41])=[CH2:39])[CH:35]=[C:34]([Cl:44])[C:33]=1[F:45]>CN(C=O)C>[Cl:31][C:32]1[CH:37]=[C:36]([C:38]2([C:40]([F:43])([F:42])[F:41])[O:1][N:2]=[C:3]([C:4]3[N:9]=[CH:8][C:7]4[C:10]5([CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]5)[O:11][CH2:12][C:6]=4[CH:5]=3)[CH2:39]2)[CH:35]=[C:34]([Cl:44])[C:33]=1[F:45]

Participants

5

Reactant 3

HCID 31398ChlorosuccinimideHCID 584682331,3-Dichloro-2-fluoro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzeneHCID 137231143HCID 137231143, compound

Product 1

HCID 89996300HCID 89996300, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

To a stirred solution of tert-butyl 6′-((hydroxyimino)methyl)-1′H-spiro[azetidine-3,3′-furo[3,4-c]pyridine]-1-carboxylate (0.15 g, 0.49 mmol, 1 eq) in DMF (5.0 mL) was added NCS (84 mg, 0.63 mmol, 1.2 eq) at room temperature in dark under nitrogen atmosphere. Resulting reaction mixture was stirred at 45° C. for 1 hour. After chloro intermediate formation, 1,3-dichloro-2-fluoro-5-(1-trifluoromethyl-vinyl)-benzene (0.163 g, 0.63 mmol, 1.2 eq.) was added followed by addition of KHCO3 (79 mg, 0.79 mmol, 1.5 eq). Resulting reaction mixture was stirred at room temperature for 16 hours in dark under nitrogen atmosphere. After complete consumption of chloro intermediate, reaction mixture was quenched with water (20 mL) and extracted with ethyl acetate (3×20 mL). Combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to get brown thick oil (0.2 g, crude). Crude compound was purified by column chromatography in 100-200 mesh size silica gel. Desired compound was eluted in 25% ethyl acetate in hexane to afford title compound as off white solid (0.14 g, 51%). 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 3.88 (d, J=18.4 Hz, 1H), 4.12-4.16 (m, 2H), 4.25 (d, J=18.16 Hz, 1H), 4.35 (dd, J1=3.3 Hz, J2=9.34 Hz, 2H), 5.12 (s, 2H), 7.57 (d, J=6 Hz, 2H), 7.90 (s, 1H), 8.70 (s, 1H). LC-MS (m/z): 562.1 (M+H).

Workup

  1. customResulting
  2. customreaction mixture
  3. customResulting
  4. customreaction mixture
  5. stirringwas stirred at room temperature for 16 hours in dark under nitrogen atmosphere
  6. customAfter complete consumption of chloro intermediate, reaction mixture
  7. customwas quenched with water (20 mL)
  8. extractionextracted with ethyl acetate (3×20 mL)
  9. dry with materialCombined organic layer was dried over anhydrous Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customto get brown thick oil (0.2 g, crude)
  12. customCrude compound was purified by column chromatography in 100-200 mesh size silica gel
  13. washDesired compound was eluted in 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-9e5a9625ce6646ad8ba23189ea23eff5
Source dataset
uspto-grants-2015_09
Patent number
US09131697B2

Reaction notes

Loading…