Triethylamine → Ethyl [1-(diphenylmethyl)azetidin-3-ylidene]acetate

HRID 1596181Notes

Reaction equation

HRID 1596181 reaction equation
[CH:1]([N:14]1[CH2:17][C:16](=O)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:26]([CH:31]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:28][CH2:29][CH3:30])=[O:27]>C(Cl)Cl>[CH2:29]([O:28][C:26](=[O:27])[CH:31]=[C:16]1[CH2:17][N:14]([CH:1]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:15]1)[CH3:30]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 70670Acetic acid, 2-(triphenylphosphoranylidene)-, ethyl esterHCID 37355581-(Diphenylmethyl)azetidin-3-one

Product 1

HCID 53428664Ethyl [1-(diphenylmethyl)azetidin-3-ylidene]acetateYield 100.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of DMSO (5.3 mL, 75 mmol) in methylene chloride (100 mL) at −78° C. under argon was added oxalyl chloride (4.6 mL, 53 mmol) dropwise. After stirring for 30 min., a solution of 1-benzhydryl-azetidin-3-ol hydrochloride (12) (10 g, 36 mmol) in methylene chloride (10 mL) was added dropwise. The reaction mixture was stirred for 1 hr at −78° C. before triethylamine (18 mL, 128 mmol) was added. The ice bath was removed and the reaction quenched with saturated ammonium chloride (75 mL) at 0° C., then extracted with ethyl acetate (3×150 mL). The combined ethyl acetate layer was washed with water (100 mL), brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was stirred in ethyl acetate and hexane, filtered to give 1-benzhydrylazetidin-3-one (9 g, 33 mmol, 92%). To a stirring solution of the resulting 1-benzhydryl-azetidin-3-one (8.3 g, 30 mmol) in methylene chloride (120 mL) was added triethylamine (6.4 mL, 45 mmol), and carbethoxymethylene triphenylphosphorane (15.9 g, 45 mmol). This reaction mixture was stirred under argon at room temperature for 2 hrs., then quenched with acetone (1 mL), and concentrated in vacuo. The residue was stirred in 20% ethyl acetate in hexane (20 mL) as triphenyl phosphine oxide precipitated. The mixture was then filtered and concentrated. The crude product was chromatographed on silica gel, eluting with 50:40:10 methylene chloride:hexane:ether to give 9.3 g of the title compound.

Workup

  1. custom, then quenched with acetone (1 mL)
  2. concentrationconcentrated in vacuo
  3. stirringThe residue was stirred in 20% ethyl acetate in hexane (20 mL) as triphenyl phosphine oxide
  4. customprecipitated
  5. filtrationThe mixture was then filtered
  6. concentrationconcentrated
  7. customThe crude product was chromatographed on silica gel
  8. washeluting with 50:40:10 methylene chloride

Sources & evidence

ORD record
ord-491185c6affa475ba49c65da8bdd3dc8
Source dataset
uspto-grants-2001_09
Patent number
US06291457B1

Reaction notes

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