Diisopropylethylamine → 7-Fluoro-2-[3-(hydroxymethyl)azetidin-1-yl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

HRID 17481Notes

Reaction equation

HRID 17481 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.[OH:30][CH2:31][CH:32]1[CH2:35][NH:34][CH2:33]1>C(Cl)Cl.C(Cl)(Cl)Cl>[F:11][C:10]1[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:8]([CH3:18])[C:7]([C:19]#[N:20])=[C:5]2[C:4]=1[O:3][C:2]([N:34]1[CH2:35][CH:32]([CH2:31][OH:30])[CH2:33]1)=[N:6]2

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 13400658(Azetidin-3-yl)methanolHCID 510414292-Chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

Product 1

HCID 685843917-Fluoro-2-[3-(hydroxymethyl)azetidin-1-yl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrileYield 74%

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) (240 mg, 0.84 mmol) was dissolved in methylene chloride (10 ml), then diisopropylethylamine (584 μl, 3.35 mmol) and 3-hydroxymethylazetidine (206 mg, 1.67 mmol) dissolved in methylene chloride (5 ml) were added, followed by heating under reflux in a sealed tube for 5 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. The eluate with chloroform/methanol (10:1, v/v) gave the entitled compound (208 mg, 74%) as a white solid.

Workup

  1. additionwere added
  2. temperatureby heating
  3. temperatureunder reflux in a sealed tube for 5 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-11a959f190a0418f82f8c70cb8972444
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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