Trifluoroacetic acid → HCID 71777794, compound

HRID 1021296Notes

Reaction equation

HRID 1021296 reaction equation
[OH:1][CH:2]1[CH2:5][N:4](C(OC(C)(C)C)=O)[CH2:3]1.[CH3:13][C:14]1[N:19]=[CH:18][C:17](O)=[CH:16][CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.C1(C)C=CC=CC=1.C(O)(C(F)(F)F)=O>ClCCCl.C1COCC1>[NH:4]1[CH2:3][CH:2]([O:1][C:17]2[CH:16]=[CH:15][C:14]([CH3:13])=[N:19][CH:18]=2)[CH2:5]1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 11776TriphenylphosphineHCID 142752-Methyl-5-hydroxypyridineHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylateHCID 178459888HCID 178459888, compound

Product 1

HCID 71777794HCID 71777794, compoundYield 31.4%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

tert-Butyl 3-hydroxyazetidine-1-carboxylate (1.0 g) and 6-methylpyridin-3-ol (570 mg) were mixed with THF (10 ml), and triphenylphosphine (2.3 g) was added thereto. A 1.9 M DIAD/toluene solution (4.5 ml) was added dropwise thereto, followed by stirring at 55° C. overnight. The reaction mixture was concentrated under reduced pressure, and EtOAc and 1 M hydrochloric acid were added thereto. The aqueous layer was adjusted to pH of around 10 by the addition of a 4 M aqueous NaOH solution, followed by extraction with CHCl3. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH). The purified product thus obtained was mixed with DCE (6 ml), and TFA (3 ml) was added thereto, followed by stirring at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure, and then CHCl3 and a 1 M aqueous NaOH solution were added thereto. The organic layer was dried over Na2SO4 and then concentrated under reduced pressure to obtain 5-(azetidin-3-yloxy)-2-methylpyridine (269 mg).

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated under reduced pressure, and EtOAc and 1 M hydrochloric acid
  3. additionwere added
  4. additionThe aqueous layer was adjusted to pH of around 10 by the addition of a 4 M aqueous NaOH solution
  5. extractionfollowed by extraction with CHCl3
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)
  9. customThe purified product thus obtained
  10. additionwas added
  11. stirringby stirring at room temperature for 5 hours
  12. concentrationThe reaction mixture was concentrated under reduced pressure
  13. additionCHCl3 and a 1 M aqueous NaOH solution were added
  14. dry with materialThe organic layer was dried over Na2SO4
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ef238fc593184994b0105586810bfcca
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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