Sodium bis(trimethylsilyl)amide → HCID 86671408, compound

HRID 2403321Notes

Reaction equation

HRID 2403321 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][N:3]=1.Cl.N[C@@H]1CC[CH2:16][CH2:15][C@H:14]1[OH:19].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C(O)(C)C.[Ni](I)I>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:15]2[CH2:14][O:19][CH2:16]2)=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 38450342-Chloropyridine-5-boronic acidHCID 12228412Cyclohexanol, 2-amino-, hydrochloride (1:1), (1R,2R)-

Product 1

HCID 86671408HCID 86671408, compoundYield 388.3%

Reagents, catalysts & solvents 2

HCID 26038Nickel(II) iodideCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-chloropyridine-5-boronic acid (315 mg, CAS 444120-91-6) in isopropanol (2 ml) in a 10 mL microwave vial were added nickel iodide (18.8 mg), trans-2-aminocyclohexanol hydrochloride (9.21 mg) and sodium bis(trimethylsilyl)amide (387 mg). Argon was bubbled into the reaction mixture for 5 min. A solution of 3-iodo-oxetane (190 mg, CAS 26272-85-5) in isopropanol (0.25 ml) was then added. The vial was then capped and heated in the microwave at 80° C. for 20 min. TLC at t=20 min showed the reaction was complete. The reaction mixture was diluted with EtOH and filtered through celite. The filter cake was washed with EtOH and the filtrate was concentrated in vacuo. The crude material was purified by flash chromatography (silica gel; gradient: 0% to 50% EtOAc in heptane) to afford 2-chloro-5-oxetan-3-yl-pyridine (40 mg, 24%) as a white solid.

Workup

  1. customArgon was bubbled into the reaction mixture for 5 min
  2. additionA solution of 3-iodo-oxetane (190 mg, CAS 26272-85-5) in isopropanol (0.25 ml) was then added
  3. customThe vial was then capped
  4. customat t=20 min
  5. additionThe reaction mixture was diluted with EtOH
  6. filtrationfiltered through celite
  7. washThe filter cake was washed with EtOH
  8. concentrationthe filtrate was concentrated in vacuo
  9. customThe crude material was purified by flash chromatography (silica gel; gradient: 0% to 50% EtOAc in heptane)

Sources & evidence

ORD record
ord-29b83b9a8210484cbdb409433afbad14
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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