Chlorosuccinimide → HCID 89996297, compound

HRID 2276048Notes

Reaction equation

HRID 2276048 reaction equation
[OH:1][N:2]=[CH:3][C:4]1[N:9]=[C:8]2[CH2:10][O:11][C:12]3([CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]3)[C:7]2=[CH:6][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]=[C:8]4[CH2:10][O:11][C:12]5([CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]5)[C:7]4=[CH:6][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 137231142HCID 137231142, compound

Product 1

HCID 89996297HCID 89996297, compoundYield 83.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

To a stirred solution of tert-butyl 2′-((hydroxyimino)methyl)-7′H-spiro[azetidine-3,5′-furo[3,4-b]pyridine]-1-carboxylate (0.520 g, 1.705 mmol, 1 eq) in DMF (12 mL) was added NCS (0.272 g, 2.046 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 (0.530 g, 2.046 mmol, 1.2 eq) was added followed by addition of KHCO3 (0.255 g, 2.557 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 (100 mL) and extracted with ethyl acetate (3×100 mL). Combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to get brown thick oil (1.2 g, Crude). Crude compound was purified by column chromatography in 100-200 mesh size silica gel. Desired compound was eluted in 10% ethylacetate in hexanes to afford title compound as white semisolid (0.800 g, impure). Impure compound was used as such for next reaction. 1H NMR (400 MHz, CDCl3) δ: 1.46 (s, 9H), 3.84 (d, J=18.2 Hz, 1H), 4.10 (dd, J1=2.54 Hz, J2=9.5 Hz, 2H), 4.22 (d, J=18.16 Hz, 1H), 4.33 (dd, J1=3 Hz, J2=9.44 Hz, 2H), 5.02-5.10 (m, 2H), 7.56 (d, J=6 Hz, 2H), 7.84 (d, J=8.04 Hz, 1H), 8.03 (d, J=8.04 Hz, 1H). LC-MS (m/z): 59.6 (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 (100 mL)
  8. extractionextracted with ethyl acetate (3×100 mL)
  9. dry with materialCombined organic layer was dried over anhydrous Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customto get brown thick oil (1.2 g, Crude)
  12. customCrude compound was purified by column chromatography in 100-200 mesh size silica gel
  13. washDesired compound was eluted in 10% ethylacetate in hexanes

Sources & evidence

ORD record
ord-b6a747b433434e07925713529d6823e1
Source dataset
uspto-grants-2015_09
Patent number
US09131697B2

Reaction notes

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