Triethylamine → CID 59594737

HRID 2263442Notes

Reaction equation

HRID 2263442 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]=[C:14]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)[S:15][C:16]=1[CH2:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[C:21]([F:27])[CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:39][OH:40].C(N(CC)CC)C>O1CCCC1.CO>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]=[C:14]([C:28]2[CH:29]=[CH:30][C:31]([C:34]([F:36])([F:35])[F:37])=[CH:32][CH:33]=2)[S:15][C:16]=1[CH2:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([C:23]([NH:39][OH:40])=[NH:24])=[C:21]([F:27])[CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 595946854-[4-(3-Benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-benzonitrile

Product 1

HCID 178513354CID 59594737Yield 69.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 0.84 g of 4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-benzonitrile in 5 mL of tetrahydrofuran and 5.6 mL of methanol were added 1.14 g of hydroxylamine hydrochloride followed by 1.8 mL of triethylamine. The reaction mixture was stirred at reflux temperature for 2 h and then at room temperature overnight. The reaction mixture was refluxed for an additional 2 h and then concentrated under reduced pressure. The residue was taken up into dichloromethane then water was added. The aqueous layer was separated and extracted three times with dichloromethane. The combined organic layers were washed with water, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 0.840 g of crude product as a yellow gum. Precipitation in heptane afforded 620 mg of 4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-N-hydroxy-benzamidine as a beige powder.

Workup

  1. temperatureat reflux temperature for 2 h
  2. customat room temperature
  3. customovernight
  4. temperatureThe reaction mixture was refluxed for an additional 2 h
  5. concentrationconcentrated under reduced pressure
  6. additionwater was added
  7. customThe aqueous layer was separated
  8. extractionextracted three times with dichloromethane
  9. washThe combined organic layers were washed with water
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customto give 0.840 g of crude product as a yellow gum
  14. customPrecipitation in heptane

Sources & evidence

ORD record
ord-2646d0bf622c49f1ba61c7ee976817e9
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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