Diisopropylethylamine → Ethyl [1-(4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazol-2-yl)azetidin-3-yl]acetate

HRID 17478Notes

Reaction equation

HRID 17478 reaction equation
Cl[C:2]1[O:3][C:4]2[C:5](=[C:7]([C:19]#[N:20])[C:8]([CH3:18])=[C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:10]=2[F:11])[N:6]=1.C(N(C(C)C)CC)(C)C.[NH:30]1[CH2:33][CH:32]([CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:31]1>C(Cl)Cl.C(Cl)(Cl)Cl>[C:19]([C:7]1[C:5]2[N:6]=[C:2]([N:30]3[CH2:33][CH:32]([CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:31]3)[O:3][C:4]=2[C:10]([F:11])=[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]=1[CH3:18])#[N:20]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 510414292-Chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrileHCID 54328202HCID 54328202, compound

Product 1

HCID 86630854Ethyl [1-(4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazol-2-yl)azetidin-3-yl]acetateYield 76.3%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent2×

Procedure

Under nitrogen atmosphere, 2-chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-cabonitrile (I-130) (400 mg, 1.40 mmol) was dissolved in methylene chloride (15 ml), then diisopropylethylamine (537 μl, 3.08 mmol) and ethyl azetidine-3-acetate (503 mg, 2.80 mmol) dissolved in methylene chloride (5 ml) were added, followed by heating under reflux for 19 hours. After cooling, diluting with chloroform and washing with water, the organic layer was dried over anhydrous magnesium sulfate, then the solvent was evaporated away under reduced pressure. The resulting residue was subjected to preparative silica gel column chromatography. From the eluate with ethyl acetate/hexane (1:1, v/v), the entitled compound (420 mg, 76%) was obtained as a colorless oil.

Workup

  1. additionwere added
  2. temperatureby heating
  3. temperatureunder reflux for 19 hours
  4. temperatureAfter cooling
  5. washwashing with water
  6. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated away under reduced pressure

Sources & evidence

ORD record
ord-fbbd76cfa78b4e5fbe82126ff45f29a3
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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