3-Methylbenzofuran → 1-Benzhydryl-3-(3-methylbenzofuran-2-yl)azetidin-3-ol

HRID 634032Notes

Reaction equation

HRID 634032 reaction equation
[CH3:1][C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH:3]=1.[Li+].CC([N-]C(C)C)C.[CH:19]([N:32]1[CH2:35][C:34](=[O:36])[CH2:33]1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1COCC1>[CH:19]([N:32]1[CH2:35][C:34]([C:3]2[O:4][C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[C:2]=2[CH3:1])([OH:36])[CH2:33]1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 889393-MethylbenzofuranHCID 2724682Lithium diisopropylamideHCID 37355581-(Diphenylmethyl)azetidin-3-one

Product 1

HCID 671545491-Benzhydryl-3-(3-methylbenzofuran-2-yl)azetidin-3-olYield 31%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-methylbenzofuran (550 mg, 4.16 mmol) in dry THF (17 mL) was cooled to −78° C. and LDA (1.8 M in THF/heptane/ethylbenzene) (2.8 mL, 5.04 mmol) was added dropwise under N2 over 5 min. After stirring for 30 min, 1-benzhydrylazetidin-3-one (1.61 g, 6.78 mmol) was added portionwise over 10 min. The reaction was stirred under N2 at −78° C. for 15 min, and was then allowed to warm to rt and stirred for 1.5 h. The reaction was quenched with 0.5N HCl and extracted with EtOAc. The organic layer was washed with water and brine, dried on Na2SO4 and concentrated. The residue was purified by flash chromatography (heptane/EtOAc, 5%->35%), yielding the product (472 mg, 31%) as a yellow oil.

Workup

  1. stirringThe reaction was stirred under N2 at −78° C. for 15 min
  2. stirringstirred for 1.5 h
  3. customThe reaction was quenched with 0.5N HCl
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with water and brine
  6. customdried on Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (heptane/EtOAc, 5%->35%)

Sources & evidence

ORD record
ord-3a1b0884b3e249f89083dfe412fc5575
Source dataset
uspto-grants-2016_04
Patent number
US09321769B2

Reaction notes

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