Diisopropylethylamine → Tert-butyl 3-(pyridin-4-ylmethoxy)azetidine-1-carboxylate

HRID 2172023Notes

Reaction equation

HRID 2172023 reaction equation
[C:1]([N:8]1[CH2:11][CH:10]([OH:12])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CC([O-])(C)C.[K+].Br.Br[CH2:21][C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1.CCN(C(C)C)C(C)C>C1COCC1.ClCCl.O>[N:25]1[CH:26]=[CH:27][C:22]([CH2:21][O:12][CH:10]2[CH2:11][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9]2)=[CH:23][CH:24]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylateHCID 127522194-(Bromomethyl)pyridine hbrHCID 23665647Potassium tert-butoxide

Product 1

HCID 67154567Tert-butyl 3-(pyridin-4-ylmethoxy)azetidine-1-carboxylateYield 41%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of N-Boc-azetidin-3-ol (500 mg, 2.89 mmol) in THF (10 mL) was cooled to 0° C. t-BuOK (1M in THF, 11.6 mL) was added dropwise and the reaction mixture was stirred at room temperature for 0.25 h then cooled to 0° C. A solution of 4-bromomethylpyridine hydrobromide (2.19 g, 8.67 mmol) in dichloromethane (5 mL) stirred with DIPEA (4 mL, 24 mmol) for 0.5 h was then added. The reaction mixture was stirred at room temperature for 24 h. The reaction mixture was diluted with H2O and extracted twice with EtOAc. The organics were separated from the aqueous layer and combined, dried over Na2SO4 and concentrated to dryness. The crude mixture was purified by column chromatography (eluent: Pentane/EtOAc, 1/1 to 7/3) to give the title product (313 mg, 41%) as a yellow oil.

Workup

  1. additionwas added dropwise
  2. temperaturethen cooled to 0° C
  3. additionwas then added
  4. stirringThe reaction mixture was stirred at room temperature for 24 h
  5. extractionextracted twice with EtOAc
  6. customThe organics were separated from the aqueous layer
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to dryness
  9. customThe crude mixture was purified by column chromatography (eluent: Pentane/EtOAc, 1/1 to 7/3)

Sources & evidence

ORD record
ord-3f8f49ec77f64e5d9b0da063ae4892ac
Source dataset
uspto-grants-2015_06
Patent number
US09051321B2

Reaction notes

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