Triethylamine → (3,5-Di-tert-butyl-4-hydroxy-phenyl)-(3-hydroxy-3-methyl-azetidin-1-yl)-methanone

HRID 1766969Notes

Reaction equation

HRID 1766969 reaction equation
Cl.[CH3:2][C:3]1([OH:7])[CH2:6][NH:5][CH2:4]1.C(N(CC)CC)C.[C:15]([C:19]1[CH:20]=[C:21]([CH:25]=[C:26]([C:29]([CH3:32])([CH3:31])[CH3:30])[C:27]=1[OH:28])[C:22](O)=[O:23])([CH3:18])([CH3:17])[CH3:16].C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[C:29]([C:26]1[CH:25]=[C:21]([C:22]([N:5]2[CH2:6][C:3]([OH:7])([CH3:2])[CH2:4]2)=[O:23])[CH:20]=[C:19]([C:15]([CH3:18])([CH3:17])[CH3:16])[C:27]=1[OH:28])([CH3:32])([CH3:30])[CH3:31]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 150073,5-Di-tert-butyl-4-hydroxybenzoic acidHCID 115427813-methylazetidin-3-ol Hydrochloride

Product 1

HCID 11278623(3,5-Di-tert-butyl-4-hydroxy-phenyl)-(3-hydroxy-3-methyl-azetidin-1-yl)-methanoneYield 73.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
25 °C

Procedure

3-Methyl-azetidin-3-ol hydrochloride (0,6 g, 4,84 mmoles) was suspended in tetrahydrofuran (50 ml) and Triethylamine (1,2 ml) was added. The mixture was stirred at room temperature (approximately 25° C.) for 30 minutes and 3,5-di-tert-butyl-4-hydroxy benzoic acid (1,26 g, 5,1 mmoles) was added in one portion, the mixture was cooled to 0° C. and subsequently a solution of dicyclohexylcarbodiimide (1 g, 4,84 mmoles) in tetrahydrofuran (27 ml) was added. The reaction mixture was then heated to reflux for 3,5 hours, cooled and the insoluble solid was filtered off. The filtrate was concentrated using a rotavapor, the remaining solid dissolved in ethyl acetate, washed with water, dried over magnesium sulfate, filtered and evaporated to dryness. The crude residue obtained is crystallized from diethyl ether to give 1,14 g (73% of theoretical yield) of (3,5-di-tert-butyl-4-hydroxy-phenyl)-(3-hydroxy-3-methyl-azetidin-1-yl)-methanone.

Workup

  1. temperaturethe mixture was cooled to 0° C.
  2. temperatureThe reaction mixture was then heated
  3. temperatureto reflux for 3,5 hours
  4. temperaturecooled
  5. filtrationthe insoluble solid was filtered off
  6. concentrationThe filtrate was concentrated
  7. dissolutionthe remaining solid dissolved in ethyl acetate
  8. washwashed with water
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. customevaporated to dryness
  12. customThe crude residue obtained
  13. customis crystallized from diethyl ether

Sources & evidence

ORD record
ord-132297c3c4c24cd2a1f5133442d3b52f
Source dataset
uspto-grants-2007_06
Patent number
US07232812B2

Reaction notes

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